Diabetes

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Amino Acids

• General Information
  • Essential Amino Acids
    • Histidine - lower blood pressure

    • Isoluecine - regulates blood sugar and energy levels

    • Leucine - lower blood sugar levels
      • Leucine has been shown to serve an important role in the metabolic pathway for insulin

    • Lycine - lower high serum triglyceride levels
      • Lysine is involved in the browning reaction, or carmelization, in foods such as
        pastries, doughnuts, cookies and cereals. In this process, lysine and sugar become
        linked together in a way that makes lysine difficult for the body to absorb. As a
        result, a diet high in cereals and baked goods, especially those that contain a lot
        of simple sugars, can result in low lysine intake.
      • Lysine supplements are considered safe and nontoxic. However, one animal study
        found that chicks fed with L-lysine developed elevated cholesterol and triglyceride
        levels.

    • Methionine - assists in the breakdown of fats

    • Phenylalamine - elevates mood and alertness

    • Threonine - maintains proper protein balance

    • Tryptophan - natural relaxant

    • Valine - muscle metabolism

  • Non-essential Amino Acids
    • Alanine - aids in the metabolism of glucose

    • Arginine - enhances immune system; aid in stimulating the pancreas to release insulin
      • Influence of arginine on splanchnic glucose metabolism in man @ diabetesjournals.org (09/22)
      • Arginine: Dosing, Safety, Interactions
        • A dose that has been studied for treating coronary artery disease is two to three
          grams taken by mouth three times daily for three to six months.
        • Other potential side effects include low blood pressure and changes in numerous
          chemicals and electrolytes in the blood. Examples include high potassium, high chloride,
          low sodium, low phosphate, high blood urea nitrogen and high creatinine levels.
        • In theory, arginine may increase the risk of bleeding.
        • Arginine may increase blood sugar levels.
      • Arginine Can Improve Your Blood Pressure @ life-enhancement.com
        • Arginine Reduces Blood Pressure in Diabetics
        • Arginine Improves Insulin Sensitivity in Type 2 Diabetics (9 grams daily)

    • Aspartic acid - rejuvenates cellular activity

    • Cysteine & Cystine - anti-oxidant; slows down the aging process

    • Glutamic acid - important in the metabolism of sugars and fats; acts as fuel for the brain
      • Injection of Glutamic Acid caused a rise in blood sugar
        • Free (not bound) glutamic acid will affect blood sugar. It interferes with insulin
          sensitivity and may contribute to diabetes.
        • Glutamic Acid and Glycine act to raise blood sugar by a sympathetic mobilization
          of glycogen

    • Glutamine - builds muscle tissue; brain fuel; decreases sugar cravings
      • Glutamine may cause constipation

    • Glycine - improves glycogen storage; promotes healthy prostate

    • Ornithine
      • Promotes the metabolism of excess body fat
      • Stimulates insulin secretion and helps insulin work as an anabolic hormone
      • Ornithine @ wikipedia.org (09/22)

    • Proline - heals skin, cartilage, tendons, and heart muscle
      • Proline @ wikipedia.org (09/22)

    • Serine - needed for proper metabolism of fats

    • Taurine - strengthens heart muscle, boosts vision
      • Taurine @ wikipedia.org (09/22)
      • Taurine Improves Insulin Sensitivity in Rats (09/22)
      • Vanadyl Sulfate and Taurine @ raysahelian.com (09/22)

    • Tyrosine - important to overall metabolism

  • Other acids
    • Carnitine
      • Carnitine @ wikipedia.org (09/22)
      • L-Carnitine Improves Glucose Disposal in Type 2 Diabetic Patients (12/08)

• Classifications of Amino Acids
  • Ketogenic Amino Acids @ wikipedia.org (09/22)
    • Ketogenic amino acids: Leucine, Lysine
    • Both ketogenic and glucogenic: Phenylalanine, Isoleucine, Threonine, Tryptophan, Tyrosine
    • Remaining 12 amino acids are exclusively glucogenic
    • Leucine has been shown to serve an important role in the metabolic pathway for insulin
    • Decreasing the intake of ketogenic amino acids lysine and threonine may induce
      hepatic steatosis, a major cause of non-alcoholic fatty liver disease

  • Ketogenic Amino Acids @ aminoco.com (09/22)
    • Essential amino acids
      • Glucogenic only
        • Histidine
        • Methionine
        • Valine
      • Either glucogenic or ketogenic
        • Isoleucine
        • Phenylalanine
        • Threonine -- (is converted to glycine)
        • Tryptophan -- supplement
      • Ketogenic
        • Leucine -- soybeans
        • Lysine -- supplement
    • Nonessential amino acids (all glucogenic)
      • Asparagine
      • Alanine
      • Glutamic acid -- egg whites, soybeans, chicken
      • Aspartic acid -- egg whites, soybeans
      • Glycine -- gelatin

• 9 Essential Amino Acids, Food Sources @ foodunfolded.com (09/22)

• Sample Foods

  Food	Serving	Calories	Protein	Keto	K or G	Gluco	Carbs
  	Size		grams	mg	mg	mg	grams
  Cashews	1 cup	786	21.0	2879	3894	14227	44.8
  Macadamias	1 cup	972	10.6	831	1963	7806	19.1
  Peanuts	1 cup	854	34.6	3482	5934	25184	31.4
  Pistachios	1 cup	699	26.3	3459	4248	18593	32.9
  Sunflower Seeds	1 cup	745	24.7	2820	4618	17262	30.8
  Soy Flour	1 cup	346	49.4	7305	9699	32396	40.3
  Gelatin	1 oz	94	24.0	1656	1308	21036	0.0
  Egg Whites, raw	1 cup	117	26.5	4427	5779	16294	1.8
  Chicken, raw	118 g	130	27.2	4359	4908	17933	0.0
  Tuna, canned	1 cup	179	39.3	6800	6832	25668	0.0
  Turkey, raw	4 oz (114 g)	170	19.9	3421	3679	12800	0.0
  Avocados	1 fruit	322	4.0	555	930	2515	17.1
  Broccoli	1 stalk	98	6.7	846	1115	4739	20.1
  Cauliflower, cooked	1 cup	29	1.1	255	331	514	5.4
  Green Beans	1 cup	27	1.6	170	234	1196	6.1
  Mushrooms	1 cup	15	2.2	159	244	1797	2.3
  Radishes, sliced	1 cup	19	0.8	74	112	614	4.0
  Spinach	1 cup	49	6.0	505	1145	4350	7.3
  Tomato Paste	1 cup	215	11.3	676	1695	8929	49.5
  Tomatoes	1 cup	27	1.3	77	197	1026	5.8
  Yellow Squash	1 cup	36	1.6	185	214	1201	7.8
  Zucchini, sliced	1 cup	29	1.2	130	149	921	7.1

• General rule:
  • 15-20% of protein is ketogenic
  • 30-40% of protein COULD be ketogenic (or glucogenic)
  • 40-55% of protein is exclusively GLUCOGENIC amino acids

• Once you reach a state of nutritional ketosis, your body can use ketones as a
  primary fuel, and make all the glucose it needs from the protein and fat that you eat.

• There is no requirement for dietary carbohydrate, because your body can make all
  the glucose it needs from the protein that you eat, or from the glycerol released when
  fatty acids are broken down.

• Jeff Volek: The Many Facets of Keto-Adaptation @ youtube.com (09/22)

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Branched Chain Amino Acids (BCAAs)

• General Information
  • BCAAs
    • Isoluecine - regulates blood sugar and energy levels
    • Leucine - lower blood sugar levels
      • Leucine has been shown to serve an important role in the metabolic pathway
        for insulin
    • Valine - muscle metabolism

  • Branched-chain amino acids (isoleucine, leucine and valine) are essential amino acids
    that account for ~35% of the essential amino acids comprising muscle proteins in humans
    and ~40% of the pre-formed amino acids required by all mammals
  • BCAA supplementation was demonstrated to preserve lean muscle mass during weight loss

• AAs Attenuate Glycemic Impairment
  • Amino Acid Mixture Attenuates Glycemic Impairment @ nih.gov (10/22)
    • Certain amino acids (AAs) have been recently demonstrated to improve glycemia and
      reduce adiposity
    • An isoleucine-enriched AA mixture (4.5% AAs; Ile: 3.0%, Leu: 1.0%, Val: 0.2%,
      Arg: 0.3% in the drinking water) of rats
    • The amino acid mixture consisting of Ile, Leu, Val, and Arg showed clear protective
      benefits on preventing the FAD-induced obesity and impaired glycemic control
    • Leucine and Isoleucine are involved in regulation of glycemic control
    • Increasing dietary leucine intake (1.5% Leu in water) has been reported to reduce
      food intake and improve glucose metabolism in mice with high-fat diet
    • Additionally, chronic supplementation of isoleucine (2-2.5% Ile in water)
      significantly reduces insulin response but not glucose level during oral glucose challenge
    • L-arginine (1.5% Arg in water) supplementation has been shown to suppress fat gain
      and to improve the metabolic profile
    • A novel amino acid mixture (leucine, isoleucine, valine, and arginine) was tested
    • Isoleucine showed greater effects on promoting muscle glucose uptake compared to
      leucine, although both isoleucine and leucine have glucose-lowering effects
    • Infusion of high-dose amino acid resulted in the development of insulin resistance
      in skeletal muscle tissue
    • Leucine can alter the energy balance toward decreasing adiposity in rodents fed
      a high-fat diet
    • Relatively lower level of AA mixture not only decreased fasting blood glucose level
      in FAD/AA rats but reduced blood HbA1c level to an approached significant state
      compared with rats fed with FAD alone

  • Hypoglycemic Effect of Isoleucine @ nih.gov (10/22)
    • Hypoglycemic Effect of Isoleucine @ journals.physiology.org (10/22)
    • Isoleucine plays an important role in the improvement of glucose metabolism as
      evidenced by the increase of insulin-independent glucose uptake in vitro
    • Oral administration of isoleucine decreased the plasma glucose level by 20% and
      significantly increased muscle glucose uptake by 71% without significant elevation
      of the plasma insulin level compared with controls at 60 min after administration
    • Isoleucine significantly inhibited glucose production when alanine was used as
      a glucogenic substrate
    • Isoleucine administration stimulates both glucose uptake in the muscle and whole
      body glucose oxidation, in addition to depressing gluconeogenesis in the liver,
      thereby leading to the hypoglycemic effect in rats
    • We hypothesized that the hypoglycemic effect of amino acids was not caused only
      by an insulinotropic effect but also by an insulin-independent effect
    • Generally, the maintenance of the blood glucose level is due to an optimal balance
      between the glucose uptake by peripheral tissues and the glucose production that
      occurs mainly in the liver
    • Glucose production is greatly affected by gluconeogenesis that occurs during the
      fasting state

  • Effect of Isoleucine Supplementation on Blood Glucose Response @ nih.gov (10/22)
    • Chronic isoleucine supplementation prevents diet-induced weight gain in rodents
    • Acute-isoleucine administration improves glucose tolerance in rodents and reduces
      postprandial glucose levels in humans
    • Chronic isoleucine supplementation may not be an effective treatment for obesity
      or glucose intolerance

  • Amino Acid Medicine @ nih.gov (10/22)
    • The branched chain amino acids (BCAAs) leucine, isoleucine, and valine are the
      most abundant of the essential amino acids
    • Leucine is the most potent of the BCAAs in stimulating muscle protein synthesis,
      while isoleucine and valine are much less effective
    • Leucine and isoleucine act as signals in glucose metabolism
    • Isoleucine stimulates both glucose uptake in the muscle and whole body glucose
      oxidation, in addition to depressing gluconeogenesis in the liver

  • Suppression of Endogenous Glucose Production by Isoleucine and Valine @ nih.gov (10/22)
    • Leucine has been shown to acutely inhibit hepatic glucose production
    • All branched-chain amino acids (BCAA) are metabolized by a shared set of enzymes
      to produce a ketoacid, which is later metabolized to acetyl-CoA
    • A high fat diet (HFD) consumption is known to interfere with central glucoregulation
    • Both isoleucine and valine individually lowered blood glucose by decreasing
      liver glucose production
    • All three BCAAs centrally modulate glucose metabolism in the liver, and their
      action is disrupted by High-Fat-Diet-induced insulin resistance

  • Contributions of Gluconeogenesis to Glucose Production in the Fasted State @ nih.gov (10/22)
    • After an overnight fast, gluconeogenesis accounts for approximately 50%, and
      after 42 h of fasting for almost all of glucose production in healthy subjects

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Essential Amino Acids

• General Information
  • Ketogenic Amino Acids @ aminoco.com (09/22)

  • 9 Essential Amino Acids, Food Sources @ foodunfolded.com (09/22)

  • Daily Requirements for 150-lb man
    The US recommended daily allowances per 2.2 pounds (1 kg) of body weight for
    the nine essential amino acids are 29 grams (Mike needs ~2000 grams)
    

    Amino Acid	Per 2.2 lbs	Per 150 lbs
    Histidine	14 mg	954 mg
    Isoleucine	19 mg	1295 mg
    Leucine	42 mg	2863 mg
    Lysine	38 mg	2591 mg
    Methionine (+ cysteine)	19 mg	1295 mg
    Phenylalanine (+ tyrosine)	33 mg	2250 mg
    Threonine	20 mg	1364 mg
    Tryptophan	5 mg	341 mg
    Valine	24 mg	1636 mg

• Supplements Only, No Food
  • Histidine: 500 mg capsules: 2 per day
  • Isoleucine (BCAA): 500 mg capsules; 3 per day (amazon.com)
  • Leucine (BCAA): 500 mg capsules: 6 per day
  • Lysine: 500 mg capsules; 6 per day
  • Methionine: 500 mg capsules: 3 capsules per day
  • Phenylalanine: 500 mg capsules: 5 capsules per day
  • Threanine: 525 mg capsules: 3 capsules per day
  • Tryptophan: 500 mg capsules: 1 per day
  • Valine (BCAA):
    • BCAAs (Leucine - 1200 mg; Valine: 600 mg; Isoleucine: 600 mg): 9 capsules per day

• Food

  Amino Acid	Required	Cashews	Macadamia	Peanuts	PB
  		(1 cup)	(1 cup)	(1 cup)	(2 tbsp)
  Histidine	954 mg	547 mg	261 mg	874 mg	175 mg
  Isoleucine	1295 mg	1001 mg	421 mg	1216 mg	194 mg
  Leucine	2863 mg	1760 mg	807 mg	2241 mg	486 mg
  Lysine	2591 mg	1119 mg	24 mg	1241 mg	214 mg
  Methionine+Cysteine	1295 mg	763 mg	31 mg	869 mg	156 mg
  Phenylalanine+Tyrosine	2250 mg	1757 mg	1576 mg	3198 mg	638 mg
  Threonine	1364 mg	811 mg	496 mg	1184 mg	165 mg
  Tryptophan	341 mg	325 mg	90 mg	336 mg	73 mg
  Valine	1636 mg	1425 mg	486 mg	1450 mg	246 mg

  Amino Acid	Required	Pistachios	Sunflower	Gelatin	Egg Whites
  		(1 cup)	(1 cup)	(1 tbsp)	(1 cup)
  Histidine	954 mg	648 mg	686 mg	46 mg	705 mg
  Isoleucine	1295 mg	1150 mg	1238 mg	81 mg	1606 mg
  Leucine	2863 mg	1988 mg	1802 mg	172 mg	2469 mg
  Lysine	2591 mg	1471 mg	1018 mg	242 mg	1958 mg
  Methionine+Cysteine	1295 mg	888 mg	1028 mg	42 mg	1666 mg
  Phenylalanine+Tyrosine	2250 mg	1889 mg	1993 mg	124 mg	1778 mg
  Threonine	1364 mg	860 mg	1009 mg	103 mg	1091 mg
  Tryptophan	341 mg	349 mg	378 mg	0 mg	304 mg
  Valine	1636 mg	1584 mg	1428 mg	146 mg	1966 mg

  Amino Acid	Required	Soy Flour	Chicken	Mushrooms	EAAs
  		(1/2 cup)	(1 oz)	(1 cup)	(4 tsp)
  Histidine	954 mg	666 mg	201 mg	40 mg	660 mg
  Isoleucine	1295 mg	1198 mg	341 mg	53 mg	1660 mg
  Leucine	2863 mg	2010 mg	485 mg	84 mg	3300 mg
  Lysine	2591 mg	1643 mg	549 mg	75 mg	2265 mg
  Methionine+Cysteine	1295 mg	730 mg	262 mg	30 mg	930 mg
  Phenylalanine+Tyrosine	2250 mg	2222 mg	475 mg	90 mg	1200 mg
  Threonine	1364 mg	1072 mg	273 mg	75 mg	1350 mg
  Tryptophan	341 mg	358 mg	76 mg	24 mg	270 mg
  Valine	1636 mg	1232 mg	321 mg	162 mg	1660 mg

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Glycine

• Glycine Metabolism and Its Alternations in Obesity and Metabolic Diseases (PDF)

• Glycine-Insulin Autocrine Feedback Loop Enhances Insulin Secretion @ diabetesjournals.org (09/22)

• Impaired "Glycine"-mia in Type 2 Diabetes @ academic.oup.com (09/22)
  • Circulating glycine levels are consistently low in patients with Type II Diabetes
  • Dietary glycine supplementation increases insulin, reduces systemic inflammation,
    and improves glucose tolerance
  • Glycine, a neurotransmitter, also acts directly on the pancreas, the brain,
    and liver glucose output
  • Elevation of branched chain amino acids (BCAAs) may play a causative role in
    insulin resistance
  • A drop in circulating glycine may be an early indicator of Type II Diabetes
  • Glycine, a “nonessential” amino acid, is consistently and negatively associated
    with T2D
  • Overweight and obese individuals have lower circulating levels of glycine
  • Lower glycine concentrations are negatively associated with insulin resistance
    and are predictive of T2D
  • Glycine supplementation enhances insulin responses and glucose tolerance
  • Glycine supplementation is sufficient to increase brain/CSF glycine in humans

• Metabolic Response to Ingested Glycine @ nih.gov (09/22)
  • Oral glycine stimulates the secretion of a gut hormone that potentiates the
    effect of insulin on glucose removal from the circulation

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Glycine, Glutamic Acid, & Phenylalanine

• General Information
  • Glutamic acid
    • Characteristics
      • Is a nonessential amino acid
      • Is a glucogenic amino acid
      • Important in the metabolism of sugars and fats
      • Acts as fuel for the brain

    • Injection of Glutamic Acid caused a rise in blood sugar
      • Free (not bound) glutamic acid will affect blood sugar. It interferes
        with insulin sensitivity and may contribute to diabetes
      • Glutamic Acid and Glycine act to raise blood sugar by a sympathetic
        mobilization of glycogen

    • Oral Glutamine Increases Circulating GLP-1, Glucagon and Insulin Levels @ nih.gov (10/22)

  • Glycine
    • Is a nonessential amino acid
    • Is a glucogenic amino acid
    • Improves glycogen storage
    • Promotes healthy prostate

  • Phenylalanine
    • Is an essential amino acid
    • Is either a ketogenic or glucogenic amino acid
    • Elevates mood and alertness

  • Glucagon
    • Glucagon
      • Glucagon is a hormone that is secreted by the pancreas, and it opposes insulin
      • Glucagon keeps blood glucose from dipping too low
      • Glucagon released is affected by amino acids, free fatty acids, and other hormones
      • High-protein and low-carb diets can increase fasting glucagon levels by ~35%

    • Glucagon-stimulating Activity of 20 Amino Acids in Dogs @ nih.gov (10/22)
      • 17 of the 20 amino acids caused a substantial increase in plasma glucagon
      • Asparagine had the most glucagon-stimulating activity (GSA), followed by
        glycine, phenylalanine, serine, aspartate, cysteine, tryptophan, alanine,
        glutamate, threonine, glutamine, arginine, ornithine, proline, methionine,
        lysine, and histidine
      • Only valine, leucine, and isoleucine failed to stimulate glucagon secretion,
        and isoleucine may have reduced it
      • No relationship between glucagon-stimulating activity and insulin-stimulating
        activity was observed

    • Modeling the Amino Acid Effect on Glucagon Secretion @ nih.gov (10/22)
      • Type 2 Diabetes Mellitus is a bi-hormonal disease caused by glucagon excess
        and insulin deficiency
      • Studying the mechanisms of glucose-stimulated insulin secretion by beta cells
        is shifting to studying the glucagon-producing alpha cells
      • Glucose inhibits glucagon secretion by a direct effect on alpha cells
      • Alpha cells respond to various stimuli, such as free fatty acids (FFAs) and
        amino acids (AAs)
      • Several studies established a strong link between AA and glucagon metabolism
      • AAs induce glucagon secretion directly
      • Alanine has a potent effect on glucagonemia, which is not surprising since
        it is the primary AA derived from proteolysis in muscle
      • The most potent AA in postprandial stimulation of glucagon secretion is most
        likely glutamate
      • Glutamine, the precursor of glutamate, is the AA preferred for transport in
        the blood, and is the most abundant
      • While the ingestion of a protein-rich meal elicits an increase of virtually
        all AAs, the increase in absolute glutamine concentration is the greatest
      • AAs play an essential role in triggering the glucagon response of pancreatic
        alpha cells
      • Between the extreme high-glucose-low-AA and low-glucose-high-AA states,
        the glucagon secretion rate can increase up to ~7-fold
      • AAs may play a similar or even more critical role than glucose in responding
        to metabolic status
      • AA-induced glucagon secretion could signal the liver to further accelerate
        gluconeogenesis because of the increased availability of AAs, especially alanine

• Alanine, Aspartic Acid, Glutamine, Glycine, and Phenylalanine in Food

  Food	Serving	ALA	ASP	GLU	GLY	PHEN
  Almonds	1 cup	1435mg	3918mg	7415mg	2104mg	1646mg
  Cashews	1 cup	962mg	2062mg	4965mg	1100mg	1084mg
  Macadamia	1 cup	520mg	1473mg	3038mg	608mg	891mg
  Peanuts	1 cup	1374mg	4216mg	7226mg	2084mg	1792mg
  Pepitas	1 cup	3530mg	7555mg	13158mg	5478mg	3727mg
  Pistachios	1 cup	1177mg	2322mg	4883mg	1219mg	1358mg
  Sunflower	1 cup	1213mg	2658mg	6060mg	1587mg	1270mg
  Almond Butter	2 tbsp	223mg	555mg	1402mg	292mg	263mg
  Cashew Butter	2 tbsp	259mg	552mg	1332mg	294mg	290mg
  Peanut Butter	2 tbsp	290mg	967mg	1613mg	455mg	380mg
  Egg Whites	1 cup	1711mg	2965mg	3767mg	1004mg	1667mg
  Gelatin	1 oz	2242mg	1474mg	2451mg	5334mg	486mg
  Parmesan Cheese	1 cup	1163mg	2673mg	8697mg	759mg	2081mg
  Soy Flour	1/2 cup	1163mg	3104mg	4780mg	1142mg	1288mg
  Beef, ground	150 gm	1954mg	2697mg	4451mg	2301mg	1192mg
  Chicken, raw	150 gm	1890mg	3087mg	5182mg	1699mg	1373mg
  Pork, ground	150 gm	1475mg	2349mg	3961mg	1202mg	1011mg
  Tuna, raw	150 gm	2116mg	3582mg	5222mg	1680mg	1366mg
  Turkey, raw	150 gm	2187mg	3432mg	5765mg	1754mg	1402mg
  Cauliflower, raw	1 cup	104mg	232mg	264mg	64mg	71mg
  Green Beans, canned	1 cup	72mg	217mg	159mg	55mg	57mg
  Mushrooms	1 cup	139mg	137mg	240mg	64mg	60mg
  Spinach, canned	1 cup	297mg	505mg	723mg	282mg	272mg
  Tomatoes, Cherry	1 cup	40mg	201mg	642mg	28mg	100mg
  Tomato Paste	1 cup	349mg	1732mg	5528mg	249mg	859mg

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Glucagon

• Glucagonocentric Restructuring of Diabetes @ nih.gov (10/22)
  • The hormone glucagon has long been dismissed as a minor contributor to
    metabolic disease
  • Here we propose that glucagon excess, rather than insulin deficiency, is
    the sine qua non of diabetes
  • Glucose-responsive Beta cells normally regulate juxtaposed Alpha cells and
    that without intraislet insulin, unregulated Alpha cells hypersecrete glucagon,
    which directly causes the symptoms of diabetes
  • This indicates that glucagon suppression or inactivation may provide therapeutic
    advantages over insulin monotherapy

• Glucagon, Dietary Protein, and Low-Carbohydrate Diets @ wholehealthsource.blogspot.com (09/22)
  • Glucagon is an hormone secreted by the pancreas; glucagon opposes insulin
  • Glucagon's main job is to keep blood glucose from dipping too low by making sure
    the liver releases enough glucose
  • Glucagon release counterbalances insulin, preventing hypoglycemia when we
    eat a high-protein meal
  • Glucagon does more or less cancel out insulin's effect on blood glucose, and eating
    protein in isolation does not lead to major changes in blood glucose
  • When glucagon is secreted, it goes to the liver first
  • Glucagon also acts directly in the brain to regulate blood glucose

• Glucagon @ my.clevelandclinic.org (09/22)
  • People with Type 2 diabetes may have glucagon levels that are relatively higher
    than what would be considered normal based on blood glucose levels. This can
    contribute to higher blood sugars.
  • Conditions that can affect your glucagon function:
    • Pancreatitis (inflammation of the pancreas)

• Glucagon: High & Low Levels + Normal Range @ labs.selfdecode.com (09/22)
  • Glucagon raises blood sugar levels, increases satiety and helps burn fats
  • Glucagon release is also influenced by the nervous system, amino acids, free
    fatty acids, and other hormones
  • Glucagon can be low in both type 1 and advanced type 2 diabetes
  • High-protein and low-carb diets can increase fasting glucagon levels by ~35%
  • High protein diets also increase insulin, a rare case when both glucagon and
    insulin are increased
  • Insulin and glucagon both tell the liver to make more glucose from non-carb
    sources (such as amino acids)
  • Stress causes the pancreas to release more glucagon (and less insulin), which
    increases glucose levels
  • Insulin resistance and high-stress hormones (including cortisol and epinephrine)
    also increase glucagon and blood glucose
  • People with inflamed pancreas had increased glucagon levels, especially during
    the initial inflammatory attack
  • Ways to decrease glucagon levels
    • Avoid prolonged fasting
    • Make sure your diet is well balanced; high protein diets can increase
      glucagon levels
    • Losing weight can help decrease glucagon levels
    • Manage stress in your life

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Glucagon-like Peptide 1 (GLP-1)

• Glucagon-like Peptide 1 (GLP-1)
  • Glucagon-like Peptide 1 @ wikipedia.org (10/22)
    • Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone
    • It is produced and secreted by intestinal enteroendocrine L-cells and certain
      neurons within the brainstem upon food consumption
    • GLP-1 stimulates insulin release and inhibits glucagon release
    • The action of GLP-1 is preserved in patients with type 2 diabetes
    • Endogenous GLP-1 is rapidly degraded, resulting in a half-life of approximately
      2 minutes
    • Consequently, only 10–15% of GLP-1 reaches circulation intact, leading to fasting
      plasma levels of only 0–15 pmol/L
    • To overcome this, GLP-1 receptor agonists and DPP-4 inhibitors have been developed
      to increase GLP-1 activity

  • Glucagon-like Peptide 1 (GLP-1) @ nih.gov (great article) (10/22)
    • A factor was found that antagonizes insulin's effect; it was named "the glucose
      agonist", or "glucagon"
    • Glucagon stimulates glycogenolysis and gluconeogenesis in the liver, and
      stimulates insulin secretion
    • Native GLP-1 has a very short half-life, which is around 1–2 min
    • In humans, fasting systemic plasma concentrations of “total” GLP-1 (including
      metabolites generated by DPP-4-mediated degradation) are typically in the range of
      5–10 pmol/L and can increase up to 40 pmol/L in response to a meal
    • Plasma systemic concentrations of “intact”, biologically active GLP-1 are much
      lower (fasting: < 2 pmol/l, peak post-nutrient concentrations 5–10 pmol/l)
    • Nutrients stimulating GLP-1 secretion include the metabolizable monosaccharides
      (glucose, fructose, and galactose), non-metabolizable monosaccharides, long-chain
      fatty acids, proteins, and certain amino acids
    • In healthy humans, ingestion of carbohydrates or proteins elicits a rapid increase
      in circulating GLP-1 with a peak 30–60 min following nutrient intake, whereas ingestion
      of lipids elicits a somewhat later but more prolonged (>120 min) increase
    • There is controversy as to whether glucose-induced GLP-1 secretion is disturbed
      in patients with type-2 diabetes
    • A possible role of intestinal sweet-taste receptors in glucose-stimulated GLP-1
      secretion remains uncertain. In isolated human L-cell cultures, glucose, and sucralose
      each stimulates GLP-1 secretion
    • Fructose given orally is a far less potent GLP-1 secretagogue related to glucose
    • L-cells, like other enteroendocrine cells, sense dietary lipids and protein
    • L-cell responds to free fatty acids and 2-monoacyl glycerol
    • Dose-dependent fatty acid-induced GLP-1 secretion is evident with Alpha-linolenic
      acid (C18:3), docosahexanoic acid (C22:6), and palmitoleic acid (C16:1)
    • Dose-dependent fatty acid-induced GLP-1 secretion is less effective with
      oleic acid (C18:1), stearic acid (C18:0), and octanoic acid (C8:0)
    • In humans, unsaturated are more effective than saturated fatty acids
    • The other main metabolite from dietary triglycerides, 2-MAG, is also a very powerful
      GLP-1 secretagogue
    • In healthy human volunteers, a diet with 30% kcal from protein (40% carbohydrates,
      30% fat) causes greater GLP-1 secretion than a diet with 10% kcal protein
      (60% carbohydrates, 30% fat)
    • Protein-stimulation of GLP-1 secretion has also been demonstrated in humans,
      with similar GLP-1 responses upon uptake of whey, casein, gluten or cod protein
    • Protein-induction of GLP-1 secretion seems to be dose-dependent, as demonstrated
      by uptake of isocaloric diets comprising 14%, 25%, or 50% of energy coming from proteins
    • Individual amino acids stimulating GLP-1 secretion include glutamine, asparagine,
      phenylalanine, and glycine, with glutamine and glycine being the most potent
    • GLP-1 inhibition of glucagon secretion is equally important for lowering
      blood glucose as GLP-1 stimulation of insulin release

  • GLP-1 Agonists @ mayoclinic.org (10/22)
    • A class of type 2 diabetes drugs is commonly called glucagon-like peptide 1
      (GLP-1) agonists
    • Studies have found that all GLP-1 drugs can lead to weight loss
    • These drugs mimic the action of a hormone called glucagon-like peptide 1
      When blood sugar levels start to rise after someone eats, these drugs stimulate
      the body to produce more insulin. The extra insulin helps lower blood sugar levels.
    • Doctors do know that GLP-1s appear to help curb hunger
    • These drugs also slow the movement of food from the stomach into the small
      intestine

• Herbs
  • Weight-Loss Herbal Formula RCM-107 @ nih.gov (10/22)
    • Glucagon-like peptide-1 (GLP-1) is one of the "satiety signals" that reduces hunger.
      It is known as an incretin hormone, secreted by enteroendocrine L cells in the
      gastrointestinal tract.
    • The amount of GLP-1 secretion is in response to calorie intake. It can be stimulated
      by both fats and carbohydrates, while protein has only a minor impact.
    • The GLP-1 receptor is located in the hypothalamus, gastrointestinal tract, and pancreas
    • Natural products such as epigallocatechin gallate (green tea), geniposide,
      berberine (Barberry, Oregon Grape), and ginsenoside metabolite compound K (Ginsing)
      have been shown to stimulate GLP-1 secretion in in vitro experiments

• Fenugreek Seed
  • Isolation of Positive Modulator of Glucagon-like Pepetide-1 Signaling from Fenugreek Seed @ nih.gov (10/22)
    • Ethanol extracts from fenugreek seeds enhanced GLP-1 signaling
    • N55 specifically enhanced GLP-1 potency more than 40-fold
    • N55 binds to GLP-1 peptide and facilitates trypsin-mediated GLP-1 inactivation

  • Fenugreek Compound (N55) Lower Plasma Glucose @ nature.com (10/22)
    • N55 was found to dose-dependently lower plasma glucose in non-fasted mice
      but not in the fasted mice
    • N55 lowers plasma glucose according to prandial status by enhancing the
      response of physiological levels of GLP-1 and is much less likely to disrupt
      tight regulation of GLP-1R signaling as compare to GLP-1 analogues

  • In Vitro Effect of Fenugreek Extracts @ hindawi.com (10/22)
    • Fractions appear to have a glucagon-antagonist effect

  • Revisiting Fenugreek @ nih.gov (10/22)
    • Taking fenugreek and metformin at the same time boosted the metformin
      bioavailability and reduced the drug distribution volume by 70%

  • Effects of Fenugreek Extract on Metformin @ nih.gov (10/22)
    • Metformin (MET) is a first-line antidiabetic drug
    • Concomitant administration of fenugreek extract with metformin maintains lower
      blood glucose levels than metformin alone
    • Concurrent administration of fenugreek significantly increased the bioavailability
      of metformin and doubled the time required to reach the peak plasma concentration
    • The volume of drug distribution decreased by about 70%, while its rate of clearance
      decreased by about 55.96%
    • The administration of fenugreek in combination with metformin significantly affected
      the pharmacokinetics of metformin
    • 4-hydroxyisoleucine, a novel amino acid in fenugreek extract, facilitates insulin
      secretion
    • Fenugreek will increase the extent of absorption of metformin

  • Fenugreek @ Herbs

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Gluconeogenesis

• General Information
  • Gluconeogenesis generates glucose from fat and protein
  • Gluconeogenesis takes place in the liver
  • Your kidneys can boost blood sugar by converting glutamine into glucose
  • Fats consist of glycerol and fatty acids
  • Glycerol can be used to make glucose
  • Fatty acids are converted into acetyl CoA
  • Your body can make glucose from all the amino acids except lysine and leucine

• Dietary Protein and the Blood Glucose Concentration @ nih.gov (08/22)
  • Approximately 32–46 g of high-quality dietary protein/day is required to
    maintain protein balance
  • The excess food-derived amino acids then are oxidized as fuel directly, or
    indirectly after conversion to glucose
  • For most common proteins, 50–80 g of glucose can be derived from 100 g of
    ingested protein

• Contributions of Gluconeogenesis to Glucose Production in the Fasted State @ nih.gov (10/22)
  • After an overnight fast, gluconeogenesis accounts for approximately 50%, and
    after 42 h of fasting for almost all of glucose production in healthy subjects

• Glycolysis and Gluconeogenesis @ amboss.com (09/22)
  • In gluconeogenesis glucose is synthesized from noncarbohydrate precursors
    such as glucogenic amino acids (mainly alanine and glutamine), odd-chain fatty acids,
    glycerol, pyruvate, and lactate
  • All amino acids, except for leucine and lysine, can be used as substrates for
    gluconeogenesis
  • Gluconeogenesis occurs almost exclusively in the liver
  • Fructose 1,6-bisphosphatase is the rate-limiting enzyme for gluconeogenesis
  • The metabolism of glucose is mainly controlled by hormones such as insulin (which
    stimulates glycolysis) and glucagon (which stimulates gluconeogenesis)
  • Sites of gluconeogenesis
    • Primarily carried out in the liver
    • Renal cortex
    • Intestinal epithelium

• How Can Eating Excess Protein Raise Blood Glucose (gluconeogenesis) (09/22)

• Whey Protein Isolate raised my blood sugar level (09/22)

• Insulin Response, It Comes from Eating Protein Too @ thestrongkitchen.com (09/22)
  • Eating carbs causes an insulin release; protein causes a similar response
  • The type of insulin response varies depending on the protein food source
  • Different proteins are digested and absorbed at different rates
  • Whey protein is absorbed much faster from the digestive tract than casein
  • Foods like meat and eggs are low on the glycemic index, but measure high on the
    insulin index
  • In non-diabetics the insulin response to protein is usually only 20-30% of the
    response you would get from an equal dose of glucose. In diabetics, however, the
    insulin response to protein can be as high as 94% of the equivalent glucose response.
  • Protein also stimulates glucagon, an antagonist to insulin, which can raise
    blood sugar

• High Levels of Fat
  • High levels of fat in the blood affect the body’s ability to clear sugar from
    the blood as well

  • Dosing Insulin for Dietary Fat: How Fat Affects Your Blood Sugar @ diabetesstring.com (09/22)
    • Dietary fat and protein affect your blood sugar
    • A meal containing 8 grams of fat won’t have a noticeable impact on your blood sugar
      levels, but eating more than 15 grams of fat in one sitting or short period of time
      will absolutely create some trouble
    • Dietary fat slows down the digestion of carbohydrates
    • When you eat a meal containing 30 or more grams of fat, that high-fat content can
      actually impact your blood sugar for up to 12 hours
    • Normally, your liver produces a very small amount of glucose all day long, 24 hours a day
    • When you eat a very large amount of fat, your liver produces more glucose because of
      insulin resistance. Your liver senses heightened levels of insulin resistance due to the
      large fat quantity and try to balance this by producing more glucose.
    • In people with diabetes, it means we need to take more insulin for sometimes up to
      12 hours after a very fatty, heavy meal.

• High Levels of Protein
  • Protein: Metabolism and Effect on Blood Glucose Levels @ nih.gov (09/22)
    • Fat has little, if any, effect on blood glucose levels, although a high fat intake
      does appear to contribute to insulin resistance
    • Protein has a minimal effect on blood glucose levels with adequate insulin
    • With insulin deficiency, gluconeogenesis proceeds rapidly and contributes to an
      elevated blood glucose level

  • Effects of Free Fatty Acid Elevation on Postabsorptive Endogenous Glucose
    Production and Gluconeogenesis in Humans @ nih.gov (09/22)
    • High plasma Free Fatty Acid concentrations increase the percent contribution
      of gluconeogenesis to endogenous glucose production, and may contribute to
      increased rates of gluconeogenesis in patients with type 2 diabetes

  • Direct and Indirect Effects of Amino Acids on Hepatic Glucose Metabolism in Humans @ nih.gov (09/22)
    • The study was designed to examine the contribution of direct (substrate-mediated)
      and indirect (hormone-mediated) effects of amino acids on hepatic glucose metabolism
      in healthy men
    • Somatostatin was used to inhibit endogenous hormone release
    • Conditions of postprandial amino acid elevation stimulate secretion of insulin and
      glucagon without affecting glycaemia despite markedly increased gluconeogenesis.
    • Impaired insulin secretion unmasks the direct gluconeogenic effect of amino acids and
      increases plasma glucose.

  • Dietary Protein Contribute Little to Glucose Production, Even Under Optimal
    Gluconeogenic Conditions in Healthy Humans @ nih.gov (09/22)

• Dynamic Adaptation of Nutrient Utilization in Humans @ nature.com (08/22)

• Fuel Sources @ pressbooks-dev.oer.hawaii.edu (09/22)

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Fats

• General Information
  • Eating Healthy Fats in Place of Carbs or Saturated Fats @ sciencedaily.com (10/22)
    • Our findings support preventing and treating these diseases by eating more
      fat-rich foods like walnuts, sunflower seeds, soybeans, flaxseed, fish, and other
      vegetable oils and spreads, in place of refined grains, starches, sugars, and
      animal fats
    • For each five percent of dietary energy switched from carbohydrates or saturated
      fats to mono- or polyunsaturated fats, there is an approximately 0.1 percent
      reduction in HbA1c, a blood marker of long-term glucose control

  • Impact of Fat Intake on Blood Glucose Control in Type 1 Diabetes @ nih.gov (10/22)
    • High fat meals are followed by delayed and prolonged hyperglycemia and higher
      glycated hemoglobin A1c levels have been frequently reported in individuals with
      T1D consuming high amounts of fat
    • Carbohydrate intake should be 45–50% of total daily energy intake, fat intake
      no greater than 30–35% (saturated fat < 10%), and protein intake 15–20%
    • An additive effect was reported when consuming high fat and high protein meals
      together
    • Favoring either carbohydrate or fat over protein or favoring carbohydrate for fat
      were associated with higher glycemic excursions
    • Finally, in adults with T1D, fat intake negatively correlated with time spent in
      euglycemia and positively correlated with time spent in hyperglycemia

• Coconut Oil
  • Are We Going Nuts on Coconut Oil? @ nih.gov (10/22)

  • Can You Eat Coconut Oil if You Have Diabetes @ healthline.com (10/22)
    • Lauric acid, the main MCT found in coconut oil, is digested and absorbed very
      slowly and behaves more like a LCT in the body

  • The Glucose-Lowering Effects of Coconut Oil @ hindawi.com (10/22)
    • Coconut oil is a saturated fat comprised mostly (>60%) of the medium-chain
      fatty acid, lauric acid (50%), with smaller amounts of myristic and palmitic acid
    • Lauric acid is a saturated fatty acid (SFA) with a structure that is C12:0,
      classifying it as a medium-chain fatty acid (MCFA)
    • MCFAs differs from other fatty acids as they are hydrolyzed and absorbed faster
      than other fats
    • MCFAs do not undergo degradation and re-esterification processes, and can be
      directly used in the body to produce energy
    • There is a preferential metabolism of MCFAs over LCFAs
    • We present a case of a 66-year-old man with a history of type 2 diabetes managed
      with insulin who developed recurrent hypoglycemia and required reduction in insulin
      therapy quickly after consuming coconut oil supplementation

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Protein Quality

• General Information
  • Complete protein contain all 9 essential amino acids; incomplete proteins are
    missing one or more amino acids
  • Essential amino acids: histidine, isoleucine, leucine, lysine, methionine,
    phenylalanine, threonine, tryptophan, and valine
  • Animal products (chicken, eggs, dairy, and seafood) tend to be complete proteins
  • Incomplete proteins tend to be plant-based
  • Complete plant-based products include quinoa, buckwheat, and soy
  • Legumes such as lentils, beans, edamame/soybeans as well as nuts, seeds and
    whole grains are good vegetarian sources of protein

• The Protein Digestibility-Corrected Amino Acid Score @ academic.oup.com (08/22)
  • Amount of protein needed to upgrade 1 gram of wheat protein to obtain the lysine
    requirement level of 58 mg/g mixed crude protein
    • Beef: 1.0 gram
    • Cow's milk: 1.6 grams
    • Egg: 2.6 grams
    • Soy: 6.2 grams

• Protein Digestibility-Corrected Amino Acid Score @ nih.gov (08/22)

• Protein Digestibility Corrected Amino Acid Score @ wikipedia.org (08/22)
  • 1.00: cow's milk, eggs, soy protein, whey
  • 0.95: chicken
  • 0.91: soy
  • 0.90: pea protein concentrate (isolate)
  • 0.75: black beans
  • 0.73: vegetables
  • 0.52: peanuts

• Digestible Indispensable Amino Acid Score @ wikipedia.org (09/22)
  • Milk Protein Concentrate: 1.10
  • Soy Protein Concentrate: 0.898
  • Chickpeas: 0.83
  • Roasted peanuts: 0.434
  • Gelatin: 0.02

• Comprehensive Overview of Quality Plant- and Animal-Sourced Proteins @ nih.gov (09/22)
  • Soy and whey proteins fall into the high‐quality protein range
  • Gelatin, corn, wheat, hemp, fava bean, oat, pea, canola, rapeseed, lupin, and
    rice proteins lie in the no quality claim category
  • Potato, soy, and pea proteins seem the most promising plant‐based complementary sources

• Protein - Which is Best? @ jssm.org (08/22)

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Ketosis

• Ketogenic Diet
  • Metabolic Effects of the Very-Low-Carbohydrate Diets @ nih.gov (09/22)
    • Insulin is not needed for glucose uptake and utilization in man
    • Both muscle fat and carbohydrate burn in an amino acid flame

  • A Ketosis Biochemistry Primer @ climbingnutrition.com (09/22)

  • The Ketogenic Diet @ climbingnutrition.com (08/22)
    • Eat less than 25 carbs a day to enter ketosis

  • Ketosis Biochemistry Primer @ climbingnutrition.com (08/22)

  • Can We Convert Fats Into Carbohydrates @ climbingnutrition.com (08/22)

  • Dietary Protein and the Blood Glucose Concentration @ nih.gov (08/22)
    • Approximately 32–46 g of high-quality dietary protein/day is required to
      maintain protein balance
    • The excess food-derived amino acids then are oxidized as fuel directly, or
      indirectly after conversion to glucose
    • For most common proteins, 50–80 g of glucose can be derived from 100 g of
      ingested protein
    • Ingested protein per se does not increase the circulating glucose concentration

  • Control of Glycaemia @ nih.gov (08/22)
    • Fasting hyperglycaemia results primarily from excessive release of glucose by
      the liver due to increased gluconeogenesis
    • Postprandial hyperglycaemia results from both impaired suppression of hepatic
      glucose release and impaired skeletal muscle glucose uptake

• Quantified Diabetes
  • 16 Sugar Substitutes Reviewed by Serious Keto @ youtube.com (08/22)

  • Allulose
    • Effects of Food Ingredients of Blood Glucose: Allulose @ quantifiedediabetes.com (08/22)

    • I Ate 50 Grams of Allulose by Black Sheep Keto @ youtube.com (08/22)

  • Erythritol
    • Serum Glucose, Insulin Levels, and Erythritol Balance After Oral Administration of Erythritol @ nih.gov (08/22)

  • Oat Fiber
    • Oat Fiber is considered to be poorly fermentable

    • Fermentation of Oat Fiber in the Rat Intestinal Tract @ nih.gov (08/22)
      • Fiber from husk was only 0.5% soluble and nearly completely resistant to fermentation
      • Fiber from bran (38% soluble) and white flour (24% soluble) was more fermentable
        (62% and 55% of the intake, respectively)
      • Fiber from commercial bran (37% soluble) was most extensively fermented; only 19%
        of the fiber could be detected in feces

    • Effects of Food Ingredients on Blood Glucose: Oat Fiber @ reddit.com (08/22)

    • Effects of Food Ingredients on Blood Glucose: Oat Fiber @ quantifieddiabetes.com (08/22)

    • "Keto" Baking Products to AVOID @ sw-ke.facebook.com (08/22)
      • Vital Wheat Gluten, Flax-Meal, Lupin Flour, CarbQuick, Tapioca Fiber, Yeast, Chia,
        Cassava Flour, OAT FIBER
      • If you want to be successful on the keto diet, you can not subtract fiber from the
        total carbohydrates to get this magic "net" carb number. You must count fiber in your
        carbohydrates.

  • Resistant Starch
    • Resistanct Wheat Starch @ quantifieddiabetes.com (08/22)
      • Resistant wheat starch increases my blood sugar by 76% that of glucose (by iAUC),
        but with a slower rise, lower peak (33% that of glucose), and much longer tail
      • Even insoluble fibers can range in impact from 0.4 - 76% of glucose

  • Whey Protein and Olive Oil
    • Whey Protein & Olive Oil @ quantifieddiabetes.com (08/22)
      • Olive oil had a negligible effect on my blood sugar
      • Whey protein isolate increases my blood sugar by ~20% that of glucose (by iAUC),
        but with a slower rise

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Adiponection

• Adiponectin
  • Adiponectin @ clevelandclinic.org (09/22)
    • Adiponectin is a hormone your adipose (fat) tissue releases that helps with
      insulin sensitivity and inflammation
    • Low levels of adiponectin are associated with several conditions, including
      obesity, Type 2 diabetes and atherosclerosis
    • Adiponectin is a hormone and an adipokine protein that affects several
      metabolic processes
    • Insulin seems to play a role in the creation (synthesis) of adiponectin
    • The hormones insulin-like growth factor (IGF-1) and growth hormone (GH)
      regulate adiponectin release in adipose (fat) tissue
    • Leptin (another adipokine) may also play a role in adiponectin regulation
    • Adiponectin plays a role in insulin sensitivity by:
      • Impacting insulin sensitivity in your skeletal muscle and liver
      • Increasing insulin release from your pancreas
      • Enhancing basal (background) glucose and insulin-stimulated glucose uptake
        in adipose (fat) tissues
      • Inhibiting (preventing) glucose production in your liver
      • Promoting fatty acid oxidation
      • Promoting fat storage in subcutaneous fat pads instead of visceral fat pads,
        liver or skeletal muscle
    • Leptin and adiponectin are both hormones, or adipokines, that your adipose
      tissue makes and releases
    • Leptin enhances metabolism and reduces appetite
    • While higher adipose tissue (body fat) mass results in elevated leptin levels,
      a higher body fat mass results in lower adiponectin levels
    • People who have insulin resistance without obesity usually have low adiponectin
      levels as well
    • Treatments for low adiponectin levels
      • Consistent exercise and healthy weight loss
      • Metformin

  • Adiponectin: A Manifold Therapeutic Target @ biomedcentral.com (08/22)
    • Adiponectin is a key component in the interrelationship between adiposity,
      insulin resistance and inflammation
    • Coffee consumption increases adiponectin levels
    • White adipose tissue is nowadays perceived as an important organ involved in
      energy homeostasis and body weight control
    • Hypoadiponectinemia is consistently associated with obesity, MS, atherosclerosis,
      CAD, T2DM
    • Visceral fat deposits are more metabolically active than their subcutaneous
      homologues
    • Adiponectin values are also systematically lower in diabetics compared to
      non-diabetics
    • Serum adiponectin is inversely related to body fat mass and to the degree of
      insulin resistance
    • Adiponectin increases the sensitivity to insulin and hampers gluconeogenesis
    • Treatment with either insulin or metformin in experimental models inhibits
      the development of hypoadiponectinemia

  • Adiponectin: Structure, Role in Diseases, and Effects of Nutrition @ nih.gov (08/22)
    • Adiponectin is a cytokine that is secreted from adipose tissues (adipokine)
    • It has a protective effect on neurons and neural stem cells
    • It is affected (i.e., significantly increased) by proper healthy nutrition
    • Adiponectin probably has a role in a range of human disorders due to its
      intrinsic instability
    • Adiponectin binds to receptors (AdipoR1 and AdipoR2) to control whole-body
      energy, inflammatory responses, insulin sensitivity, and fat burning process
    • AdipoR2 is expressed mainly in the liver
    • Blood insulin levels can regulate AdipoRs expression
    • Adiponectin promotes insulin sensitivity, promotes apoptosis in carcinogenic
      cells, and has anti-oxidant and anti-inflammatory effects
    • Adiponectin can enter the brain through peripheral circulation
    • Adiponectin contributes to the control of glucose uptake and lipids metabolism,
      by reducing gluconeogenesis and enhancing glycolysis and fatty acid oxidation
      in the liver
    • In the liver, insulin stimulates lipogenesis and glycolysis and glycogen
      synthesis, whereas adiponectin stimulates fat oxidation
    • Research has shown correlation between Alzheimer’s disease and insulin
      resistance in the brain
    • Nutrition
      • Unsaturated fatty acids stimulate the release of adiponectin

  • Beneficial Effects of Adiponectin on Glucose @ nih.gov (08/22)
    • Adiponectin reduces inflammatory cytokines and oxidative stress
    • Adiponectin has been reported to suppress both glycogenolysis and gluconeogenesis
      by reducing the rate-limiting enzymes for hepatic glucose production, such as
      glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxy kinase (PEPCK)
    • How can we increase adiponectin?
      • Weight loss and exercise
      • Resveratrol enhanced adiponectin concentrations
      • Astaxanthin (salmon, shrimp) is beneficial on adiponectin levels
      • Carotenoids and tomato juice (≥25 mg lycopene daily) increased serum adiponectin levels
      • Beta-carotene increased serum adiponectin levels
      • Fish oil increased serum adiponectin levels
      • Thiazolidinediones treatment was associated with a significant increase in
        adiponectin (80-178%)
      • Metformin treatment was associated with significantly elevated serum adiponectin

  • The Influence of Nutrition on Adiponectin @ nih.gov (08/22)
    • Dietary content of sodium was negatively correlated with adiponectin concentrations
    • Adiponectin concentrations significantly increased with the degree of body weight loss
    • Both walnuts and almonds significantly increased adiponectin concentrations
    • Diet rich in olive oil had a tendency to increase adiponectin concentrations
    • Dietary fiber has a positive effect on adiponectin
    • Higher coffee consumption was associated with higher adiponectin concentrations
    • Curcumin has a beneficial effect on adiponectin
    • Diet enriched with sesame seeds significantly increased adiponectin concentrations
      in T2DM patients

  • Adiponectin, A therapeutic Target for Obesity, Diabetes, and Endothelian Dysfunction @ nih.gov (09/22)
    • Adiponectin replacement therapy in humans may suggest potential versatile
      therapeutic targets in the treatment of obesity, insulin resistance/type 2 diabetes,
      and atherosclerosis

  • COVID 19 May Trigger Hyperglycemia by Harming Fat Cells @ news.weill.cornell.edu (08/22)
    • COVID-19, can induce hyperglycemia by disrupting fat cells' production of
      adiponectin, a hormone that helps regulate blood sugar levels
    • Doctors began finding evidence that COVID-19 is associated with hyperglycemia
      in patients who have no history of diabetes
    • Hyperglycemia in COVID-19 patients is mainly caused by insulin resistance, in which
      insulin is present, but the tissues it normally acts upon are no longer sensitive to it
    • COVID-19 ARDS patients had severe declines in blood levels of adiponectin
    • COVID-19 can infect human fat cells

  • How to Increase Adiponectin @ fivejourneys.com (08/22)
    • Fish (or omega-3) oil increased adiponectin by 14-60%
    • Fiber increase adiponectin levels by 60-115%
    • Exercise, caffeine
    • Curcumin, Raspberry Ketones, cyanidin 3-glucoside (blueberries)

• Radix Astragali
  • Elevation of Adiponectin Production by Radix Astragali @ nih.gov (09/22)
    • Astragaloside II and isoastragaloside I selectively increased adiponectin secretion
      in primary adipocytes

  • Radix Astragali @ Herbs

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DHEA

• DHEA @ mountsinai.org (09/22)
  • DHEA may make insulin and drugs used to lower blood sugar less effective,
    raising the risk of high blood sugar
  • Metformin (Glucophage) can decrease or lower the levels of DHEA in the body
  • DHEA can also interact with soy, alcohol, licorice, chromium, and fiber

• Effect of DHEA on Diabetes Melltus and Obesity @ nih.gov (written in 2018) (09/22)
  • Type 2 diabetes is a metabolic disorder that is characterized by an impaired
    capacity to secrete insulin, insulin resistance, or both
  • We investigated the effects of DHEA on glucose metabolism in animal models and
    reported decrease of liver gluconeogenesis
  • A meta-analysis in elderly men and women has found that DHEA supplementation
    has no effects on blood glucose levels

• Keto Warnings @ livestrong.com (09/22)
  • Diabetic people are advised by the Mayo Clinic to avoid DHEA supplements,
    because they can cause increased blood sugar and insulin resistance

• DHEA and 7-Keto @ dcnutrition.com (09/22)
  • A group of postmenopausal women were given 50 milligrams of DHEA daily for three
    weeks. Their insulin tissue sensitivity increased and their serum triglycerides were
    lowered, indicating improved glucose handling.

• Effect of Long-Term DHEA Treatment on Glucose Metabolism @ sciencedirect.com (09/22)

• Effect of DHEA on Biomarkers for Diabetes @ blog.designforhealth.com (09/22)
  • There was a significant decrease in fasting glucose levels with DHEA
    supplementation in doses at 50 mg per day
  • There was a more significant reduction in fasting glucose levels in individuals
    60 years of age and older
  • Several studies have demonstrated an association between low DHEA levels and
    the development of complications with type 2 diabetes

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GABA

• GABA and Blood Sugar @ lifespa.com (08/22)
  • This study suggest that the body's natural production of GABA could, on one hand,
    be mitigating stress, but, on the other hand, inadvertently raise blood sugar in those
    who are diabetic or considered obese
  • When researchers chemically blocked the production of GABA, they saw a positive
    change in blood sugar regulation in just two days
  • The brain's response to the aggressive production of GABA from the liver is high blood sugar
  • Ashwagandha supports the body's healthy formation of GABA, calms the brain, and has
    also been shown to support healthy levels of blood sugar
  • Ashwangandha crosses the Blood-Brain Barrier

• Hold the GABA @ nih.gov (08/22)
  • Gabapentin, a gamma-aminobutyric acid (GABA) analogue, has infrequently been reported
    to cause liver injury
  • Discontinuing gabapentin resulted in rapid reversal improvement in hepatocellular injury

• Increased GABA Concentrations in Type 2 Diabetes are Related to Lower Cognitive Functioning @ nih.gov (08/22)

• GABA and the Liver @ karger.com (08/22)
  • Mammalian liver contains high concentrations of GABA which are carefully regulated
    by a series of hepatic metabolic pathways and a specific sodium-dependent active
    transport system

• Critical Role of Hepatic GABA in the Metabolic Dysfunctions and Hyperphagia of Obesity @ sciencedirection.com (08/22)

• The Relevance of GABA for Diabetes @ sciencedaily.com (08/22)

• Study of GABA in Healthy Volunteers @ frontiersin.org (08/22)
  • GABA is produced by pancreatic Beta-cells in large quantities
  • Within an islet, GABA suppresses glucagon secretion by the Alpha-cells as a
    consequence of membrane hyperpolarization but, in contrast, it enhances insulin
    secretion by the Beta-cells through membrane depolarization
  • GABA also increased glucagon levels only under fasting conditions (1.3-fold,
    single dose, p < 0.05; 1.5-fold, repeated dose, p < 0.01). However, there were no
    significant differences in the insulin-to-glucagon ratio and no significant change
    in glucose levels in these healthy subjects during the study period.

• GABA Improves Liver Function and Insulin Resistance of Type 2 Diabetic Rats @ nature.com (08/22)

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Diabetes

• Diabetes
  • Blood Glucose Monitoring -- What Do the Numbers Tell You? (09/22)

  • Diabetes Treatment @ RXList.com (very good article) (09/22)

  • Anti-diabetic Drugs @ Wikipedia.org (09/22)

  • Type 2 Diabetes @ Wikipedia.org (09/22)

  • Fasting Blood Glucose
    • Normal: 70-99
    • Impared (pre-diabetes): 100-125
    • Diabetes: 126 and above

• Diabetes Types (1, 1.5, and 2.0)
  • DigitalNaturopath.com (09/22)
    • TYPE 1 Juvenile diabetes or insulin-dependent diabetes mellitus (IDDM) is an autoimmune related disease,
      usually striking between the ages of 5 and 20 years, in which patients have lost all insulin production.
    • TYPE 2 Adult onset or non-insulin dependent diabetes mellitus (NIDDM) represents 90 to 95% of all diabetes,
      and is caused by a combination of insulin resistance and a relative insulin deficiency. Physical health is key
      to this syndrome as 80% of sufferers are overweight and physically inactive.
    • TYPE 1.5 is one of several names now applied to those who are diagnosed with diabetes as adults, but who
      do not immediately require insulin for treatment, are often not overweight, and have little or no resistance
      to insulin.
      • They are found to have antibodies, especially GAD65 antibodies (glutamic acid decarboxylase),
        that attack their beta cells.
      • This sort of diabetes is sometimes called Slow Onset Type 1 or Latent Autoimmune Diabetes in Adults
        (LADA). About 15% to 20% of people diagnosed as Type 2 actually have this type. They were diagnosed
        as Type 2 because they were older.
      • Since insulin resistance is minimal or nonexistent, medications designed to reduce insulin resistance such
        as Avandia and Actos are not effective. Other medications that stimulate the pancreas to produce insulin,
        slow digestion of carbohydrates, or reduce excess glucose production by the liver are often effective in
        controlling the blood sugar for a few years.
      • One clue that people have Type 1.5 rather than Type 2 is their appearance, which is more likely though not
        always slender and physically fit. They often do not have other signs of Type 2 diabetes, such as the
        Syndrome X cluster of high TGs, low HDL or high blood pressure. Luckily, in these early stages, diabetes
        treatment is not significantly different for slow onset Type 1.5s compared to truly insulin resistant Type 2s.
        The only exception is that drugs designed to increase insulin sensitivity like the glitazones do not work
        because insulin sensitivity is normal.
      • One major benefit to this type is that when their blood sugars are controlled, people with Type 1.5 usually
        do not have the high risk for heart problems more often found with the high cholesterol and blood pressure
        seen in true Type 2 diabetes.
    • Diabetics often have low manganese levels

  • Latent Autoimmune Diabetes @ wikipedia.org (09/22)

  • The LADA Epidemic (09/22)

• Dawn Effect and Somogyi Effect (high blood sugar on waking)
  • Chronic Somogyi Effect @ wikipedia.org (09/22)

  • Dawn Effect @ wikipedia.org (09/22)

  • Dawn Phenomenon & Somogyi Effect @ isletsofhope.com (01/09)
    • Dawn Effect/Phenomenon
      • The dawn effect is an increase in insulin resistance (decrease in insulin sensitivity) caused by
        hormones released about two hours before you wake. These hormones are under the control
        of the pituitary gland in the brain. The dawn effect is also influenced by testosterone and tends
        to be more significant in men.
      • In persons with diabetes, the Dawn Effect can cause blood sugar levels to rise too high and
        lead to morning fasting hyperglycemia.
      • The Dawn Effect is the most common cause of nighttime highs.
      • The Dawn Effect is the early-morning increase in blood sugar, usually between 4 a.m. and 8 a.m.
        in persons with diabetes. It can be responsible for persistently elevated fasting blood sugar and
        HbA1c levels. It is not caused by a previous low during the night and treatment involves limiting
        fat in the diet at dinnertime and in bedtime snacks.
    • Somogyi Effect
      • The Somogyi Effect is triggered by low blood sugar that causes a release of hormones including
        glucagon that raise blood sugar too much. Low blood sugar occurs most often near an insulin peak
        so you may need to test your blood sugar levels more often for a few days to see where your lows
        are beginning.

  • Somogyi Effect @ diabetesselfmanagement.com (09/22)

  • Somogyi Effect vs Dawn Phenomenon @ dlife.com (01/09)
    • Treatment for the Somogyi Effect
      • Have a snack with protein before bedtime (nuts, cheese, etc)
      • Go to bed with a glucose level slightly higher than usual
    • Treatment for the Dawn Phenomenon
      • Exercise later in the day
      • Limit bedtime carbs, and eat a protein/fat snack (nuts, cheese, meat)
      • Eat breakfast

  • Top Two Causes of High Blood Sugar in the Morning @ ezinearticles.com (09/22)

• Tips
  • What are Normal Blood Glucose Levels?
    • Fasting blood glucose: normal is less than 110; diabetic is >= 126
    • Random blood glucose: normal is low to mid 100s; diabetic >= 200

  • Target glucose range is 80-120 before meals, and 100-140 at bedtime

  • Good blood pressure is below 130/80

  • LDL cholesterol should be below 100

  • Agents that may raise blood sugar levels include arginine, cocoa, DHEA,
    ephedra (when combined with caffeine), and melatonin

  • The American Diabetes Association recommends that people with diabetes
    keep their blood pressure below 130/80

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COVID

• Can COVID-19 Cause Diabetes? @ goodrx.com (08/22)

• COVID 19 May Trigger Hyperglycemia by Harming Fat Cells @ news.weill.cornell.edu (08/22)
  • COVID-19, can induce hyperglycemia by disrupting fat cells' production of
    adiponectin, a hormone that helps regulate blood sugar levels
  • Doctors began finding evidence that COVID-19 is associated with hyperglycemia
    in patients who have no history of diabetes
  • Hyperglycemia in COVID-19 patients is mainly caused by insulin resistance, in which
    insulin is present, but the tissues it normally acts upon are no longer sensitive to it
  • COVID-19 ARDS patients had severe declines in blood levels of adiponectin
  • COVID-19 can infect human fat cells

• What's the Link Between Covid and Diabetes? @ bloomberg.com (08/22)

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???

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Sources

• Essential Amino Acids (already mixed together)
  • BulkSupplements Essential Amino Acids @ amazon.com (1.1 lbs; $23.96) (09/22)
    • Serving size: 15 grams (4 tsp) (66 servings per container)
      • L-Leucine -- 3300 mg
      • L-Isoleucine -- 1660 mg
      • L-Valine -- 1660 mg
      • L-Lysine -- 2265 mg
      • L-Threonine -- 1350 mg
      • L-Phenylalanine -- 1200 mg
      • L-Methionine -- 930 mg
      • L-Histidine -- 660 mg
      • L-Tryptophan -- 270 mg

  • Dr Berg's Keto Essential Aminos @ amazon.com (150 tabs; $40.99) (09/22)
    • REALLY expensive for what you get
    • Each tablet is 1 gram

  • Double Wood Essential Amino Acids @ amazon.com (225 caps; $19.95) (09/22)
    • 3 capsules contain 825 mg of the amino acids (in varying amounts)

  • Double Wood Essential Amino Acids @ vitacost.com (225 caps; $19.95) (09/22)

  • Double Wood Essential Amino Acids @ doublewoodsupplements.com (triple pack; $49.95) (09/22)

  • Nutricost EAA Powder (Blue Raspberry) @ amazon.com (11.6 oz; $19.95) (09/22)
    • Each serving (scoop) contains 8 grams of EAAs
    • MUCH more BCAAs than EAAs
    • 30 servings per container; $0.66/serving

  • Nutricost EAA Powder (Unflavored) @ amazon.com (8.8 oz; $17.05) (09/22)
    • MUCH more BCAAs than EAAs

  • Pure Encapsulations Essential Aminos @ amazon.com (180 caps; $47.30) (09/22)
    • 750 mg capsule contains varying amounts of the 9 essential amino acids

  • Swanson Essential Amino Acid Complex @ swansonvitamins.com (60 caps; $9.86) (09/22)
    • 1 capsule contains 75 mg of each of the 9 essential amino acids; very low dose

• Individual Essential Amino Acids

• Capsules
  • Capsuline Size 000 Empty Gelatin Capsules @ amazon.com (1000 caps; $22.95) (09/22)

  • EZ-Cap-Fillter @ etsy.com ($27.00) (09/22)

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Testing Devices

• Lancets
  • Accu-Chek Softclix Lancing Device @ amazon.com ($20.00) (11/22)

• Meters
  • Blood GLucose Monitoring System Surveillance Program @ diabetestechnology.org (2017 study) (11/22)
    • Glucose meters that passed all the tests
      • Bayer (Ascensia) Contour Next -- best (100% compliant)
      • Roche ACCU-CHEK Aviva Plus
      • Arkray Walmart ReliOn Confirm/Micro (97% compliant)
      • CVS Advanced
      • Abbott FreeStyle Lite
      • Roche ACCU-CHEK Smart View
    • Glucose meters that DIDN'T pass all the tests
      • Arkray Walmart ReliOn Prime (92% compliant)
      • Abbott Walmart ReliOn Ultima (89% compliant)
      • Bayer (Ascensia) Contour Classic (89% compliant)

  • Best Blood Glucose Monitor @ bestseekers.com (11/22)
    • Bayer Contour Next EZ Testing Kit

  • Top 10 Best Accurate Blood Glucose Meters in 2022 Reviews @ comparabit.com (11/22)

  • Ascensia Contour Next Blood Glucose Monitoring System @ amazon.com ($19.97) (11/22)

• Control Solutions
  • Walmart ReliOn Premier Classic Control Solution
    • Call 1-855-776-0662 (7-7 am CT, 7 days a week)
    • Supplies.ReliON.com (11/22)
      • You can order free control solution every 10 weeks
      • They offer control solutions for Platinum, Premier, and PRIME
      • You can order free logbooks every 3 weeks

  • Ascensia Control Next Level 1 Control Solution @ amazon.com ($19.21) (11/22)
    • 37-46 mg/dl

  • Ascensia Control Next Level 2 Control Solution @ amazon.com ($11.65) (11/22)
    • 109-135 mg/dl; 112-139 mg/dl (value will be listed on the bottle)
    • VERY good customer comments (2017) -- good accuracy

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Bonnie's Links
created by Bonnie Lee Hill,
bonniehill@verizon.net
last modified on November 23, 2022

URL: http://www.bonniehill.net/pages/diabetes.html