Research Regarding Glucose Management

Diabetes and Other Issues

Cholesterol

Cholesterol is typically split into three categoriesUTH-1

Heart disease and stroke

Diabetes can damage blood vessels in the heart, making it harder to control blood pressure and cholesterol. This can increase the risk of heart attack and stroke.

Kidney disease

Diabetes can damage blood vessels in the kidneys, causing them to not work as well or stop working. This may require dialysis or a kidney transplant.

Vitamin D3

An essential link to track is the vitamin D wicki page.

Inflammation

There appears to be a significant connection between diabetes, systemic inflammation, cholesterol, and vitamin D3.

See The Role of Inflammation in Diabetes and Vitamin D and diabetes as an initial starting point.

Quick Summaries

Comments & Notes

Notes from Dr. Sten Ekberg

Abbreviations and Acronyms

ADAGA1C-Derived Average Glucose
CGMContinuous interstitial Glucose Monitoring
FPGFasting Plasma Glucose
IGTImpaired Glucose Tolerance
IQRInterQuartile Range
OGTTOral Glucose Tolerance Test

References:

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    Added May 17 2024:
    2010 Apr.: Real-life glycaemic profiles in non-diabetic individuals with low fasting glucose and normal HbA1c: the A1C-Derived Average Glucose (ADAG) study

    We found that 93% of participants reached glucose concentrations above the IGT threshold of 7.8 mmol/l (140 mg/dL) and spent a median of 26 min/day above this level during continuous glucose monitoring.
    Eight individuals (10%) spent more than 2 h in the IGT range. They had higher HbA1c, fasting plasma glucose (FPG), age and BMI than those who did not.
    Seven participants (9%) reached glucose concentrations above 11.1 mmol/l (199 mg/dL)during monitoring.

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    Added May 19 2024:
    2019 Oct.: Continuous Glucose Monitoring Profiles in Healthy Nondiabetic Participants: A Multicenter Prospective Study

    Results: A total of 153 participants (age 7 to 80 years) were included in the analyses.
    Mean average glucose was 98 to 99 mg/dL (5.4 to 5.5 mmol/L) for all age groups except those over 60 years, in whom mean average glucose was 104 mg/dL (5.8 mmol/L).
    The median time between 70 to 140 mg/dL (3.9 to 7.8 mmol/L) was 96% (interquartile range, 93 to 98).
    Mean within-individual coefficient of variation was 17 ± 3%.
    Median time spent with glucose levels higher than 140 mg/dL was 2.1% (30 min/d).
    Median time spent with glucose levels less than 70 mg/dL (3.9 mmol/L) was 1.1% (15 min/d).

    Conclusion: A high-protein diet containing dairy food, in particular two servings of cheese, was associated with low BMI and random glucose concentration.

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    Added May 19 2024:
    2019 Jun.: High-Protein Diet Containing Dairy Products is Associated with Low Body Mass Index and Glucose Concentrations: A Cross-Sectional Study

    Results: A total of 418 individuals were evaluated.
    The consumption of a high-protein diet (1.80 ± 0.49 g/kg/day) [.82g/lb] was found in 37.8% of individuals, which showed lower BMI, WC, TSFT and blood glucose concentrations compared to those with a low-protein diet (0.56 ± 0.18 g/kg/day)[.25g/lb or ].
    Dairy products consumption was inversely associated with:

    • blood glucose when adjusted for sex and age

      Odds Ratio (OR): 0.86; 95% CI: 0.74-0.99; p = 0.042.

    • BMI when adjusted for sex and age

      OR: 0.79, 95% confidence interval (CI): 0.68-0.93, p = 0.004

    • fiber and energy when adjusted for sex and age

      OR: 0.79; 95% CI: 0.67-0.92; p = 0.004


    Cheese consumption was inversely associated with:
    • blood glucose when adjusted for sex and age (OR: 0.73, 95% CI: 0.55-0.96, p = 0.023)
    • by sex, age, calories and fibers (OR: 0.74, 95% CI: 0.56-0.98, p = 0.036).
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    Added May 19 2024:
    2023 Apr.: Blood Glucose Monitoring
    • Normal range: 4 to 6 mmol/L or 72 to 108 mg/dL.

      In 2010 the range was 65 to 99 mg/dL.

    • Impaired fasting glucose range: 5.7 to 6.4 mmol/L or 100 to 125 mg/dL
    • Impaired oral glucose tolerance test range at two hours post 75-gram oral glucose ingestion: 7.8 to 11.0 mmol/L or 140 to 199 mg/dL
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    Added May 19 2024:
    2020 Sep.:Metformin Should Not Be Used to Treat Prediabetes
    • Approximately two-thirds of people with prediabetes do not develop diabetes, even after many years.
    • Approximately one-third of people with prediabetes return to normal glucose regulation.
    • People who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome.
    • Individuals at the highest risk for developing diabetes-i.e., those with FPG concentrations of 110-125 mg/dL (6.1-6.9 mmol/L) or A1C levels of 6.0-6.4% (42-46 mmol/mol) or women with a history of gestational diabetes mellitus-should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.
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    Added May 19 2024:
    2020 Sep.: Diabetes Care Vol. 43 Iss. 9 Metformin Should Be Used to Treat Prediabetes in Selected Individuals
    • In this issue of Diabetes Care, Dr. Mayer Davidson proposes that prescription of metformin for patients with prediabetes is inappropriate. We respectfully disagree.
    • Individuals selected for treatment with metformin should have a high likelihood of benefiting.
    • Many of these supplements including cinnamon, chromium, α-lipoic acid, and bitter melon are specifically marketed for diabetes and diabetes prevention. Allowing the marketing and sale of these unproven therapies for diabetes prevention and denying high-risk individuals metformin, a proven safe, effective, and cost-saving treatment, is wrong.
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    Added May 19 2024:
    2011 Dec.: Supplementation of Vitamin C Reduces Blood Glucose and Improves Glycosylated Hemoglobin in Type 2 Diabetes Mellitus: A Randomized, Double-Blind Study
    • In patients receiving vitamin C, reduction in fasting and postmeal blood glucose was significant at week twelve.
    • In contrast, plasma ascorbic acid levels raised significantly after twelve weeks of treatment.
    • Simultaneously after twelve weeks, significant reduction was observed in glycosylated hemoglobin
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    Added May 19 2024:
    APPENDIX AFDA SAFETY ANNOUNCEMENTS FOR METFORMIN
    • Original ALERT: U.S. Boxed Warning for Lactic Acidosis
    • 2016 FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function
    • Facts about metformin
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    Added May 19 2024:
    2021 May: Time in blood glucose range 70 to 180 mg/dL and survival rate in critically ill patients: A retrospective cohort study
    • We found that lower TIR 70–180 mg/dL was associated with a higher 28 day mortality in critically ill patients with HbA1c <6.5&
    • whereas there was no consistent association in patients with HbA1c >6.5%
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    Added May 19 2024:
    2019 Dec.: Observational study of the efficacy of prolonged-release metformin in people with prediabetesy
    • Current guidelines also support treatment of prediabetes with metformin for selected subgroups of patients
    • 686 subjects with prediabetes tested using metformin XR
    • Mean (SD) fasting plasma glucose (FPG) at baseline was 6.2 (0.4) mmol/L [111 (8) mg/dL) and was reduced by -0.55 (0.7) mmol/L [-10 (13) mg/dL] after 12 weeks
    • normalized FPG in about two-fifths of subjects
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    Added May 19 2024:
    2020 Jun.: Metformin use in prediabetes: is earlier intervention better?
    • Conclusions: Metformin XR normalized FPG in about two-fifths of subjects with prediabetes.
    • These real-world data add further support a role for metformin in the management of prediabetes, in line with current guidelines in this area.
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    Added May 20 2024:
    2011 May: Metformin and exercise in type 2 diabetes: examining treatment modality interactions
    • This study reveals several ways by which metformin and exercise therapies can affect each other.
    • By increasing heart rate, metformin could lead to the prescription of lower exercise workloads.
    • Under the tested conditions, exercise interfered with the glucose-lowering effect of metformin.
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    Added May 21 2024:
    1999 May: Metformin and exercise in type 2 diabetes: examining treatment modality interactions
    • Metformin disposition is apparently unaffected by the presence of diabetes and only slightly affected by the use of different oral formulations.
    • Metformin has an absolute oral bioavailability of 40 to 60%, and gastrointestinal absorption is apparently complete within 6 hours of ingestion.
    • An inverse relationship was observed between the dose ingested and the relative absorption with therapeutic doses ranging from 0.5 [500 mg] to 1.5 g [1500 mg], suggesting the involvement of an active, saturable absorption process.
    • Metformin is rapidly distributed following absorption and does not bind to plasma proteins.
    • No metabolites or conjugates of metformin have been identified.
    • The absence of liver metabolism clearly differentiates the pharmacokinetics of metformin from that of other biguanides, such as phenformin.
    • Metformin undergoes renal excretion and has a mean plasma elimination half-life after oral administration of between 4.0 and 8.7 hours.
    • This elimination is prolonged in patients with renal impairment and correlates with creatinine clearance.
    • There are only scarce data on the relationship between plasma metformin concentrations and metabolic effects.
    • Therapeutic levels may be 0.5 to 1.0 mg/L in the fasting state and 1 to 2 mg/L after a meal, but monitoring has little clinical value except when lactic acidosis is suspected or present.
    • When lactic acidosis occurs in metformin-treated patients, early determination of the metformin plasma concentration appears to be the best criterion for assessing the involvement of the drug in this acute condition.
    • After confirmation of the diagnosis, treatment should rapidly involve forced diuresis or haemodialysis, both of which favour rapid elimination of the drug.
    • Although serious, lactic acidosis due to metformin is rare and may be minimised by strict adherence to prescribing guidelines and contraindications, particularly the presence of renal failure.
    • Finally, only very few drug interactions have been described with metformin in healthy volunteers.
    • Plasma levels may be reduced by guar gum and alpha-glucosidase inhibitors and increased by cimetidine, but no data are yet available in the diabetic population.
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    Added May 21 2024:
    2020 Nov.: Metformin and exercise in type 2 diabetes: examining treatment modality interactions
    • Metformin has been shown to have anti-cancer effects in various hormone-sensitive tumors, such as breast cancer, pancreatic cancer, colon cancer, and prostate cancer (PCa) [nih-1, nih-2]
    • The anti-cancer effects of metformin have been postulated to be associated with low insulin level subsequent to inhibition of hepatic gluconeogenesis [ nih-3].
  15. Top
    Added May 21 2024:
    2017 Apr.: Metformin and Prostate Cancer: a New Role for an Old Drug
    • Metformin has been in clinical use for more than 50 years and has a good safety record with limited toxicity.
    • Lower cancer incidence and cancer-specific deaths have been reported among diabetics on metformin compared to diabetics on other anti-diabetic medications [nih-4, nih-5].
    • metformin has been shown to inhibit the growth of cancer xenografts [nih-6, nih-7].
    • Higher insulin and c-peptide levels have been associated with poorer outcomes in cancer patients [nih-8, nih-9].
    • metformin has been shown to be effective at reducing insulin levels, even in non-diabetic patients [nih-10].
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    Added May 29 2024:
    2018 Nov.: The Timing of Activity after Eating Affects the Glycaemic Response of Healthy Adults: A Randomised Controlled Trial
    • Poor blood glucose control is a risk factor for the development of type 2 diabetes. [16a]. and cardiovascular disease [16b ,16c ,16d], even when at subclinical levels [16e ,16f].
    • Cycling on a stationary ergometer for 45 min at 40 revolutions per min with zero resistance reduced glucose levels by 7.9 mg/dL.
    • Walking for 15 to 20 minutes immediately after eating reduces glucose levels by 27 mg/dL, but if walking stops at 8 minutes, the glucose level will be higher by about 20 mg/dL at 30 min. after stopping.
  17. Top
    Added June 1 2024:
    2018 Jun.: The Effects of Postprandial Exercise on Glucose Control in Individuals with Type 2 Diabetes: A Systematic Review
    • Exercise can reduce postprandial hyperglycemia by increasing contraction-mediated glucose uptake. In other words, muscle contractions during physical activity may reduce glucose spikes after eating.
    • There is no consensus as to when, after eating, activity should begin
    • Activity reduced the "area under the curve" of the spike:
      • Aerobic exercise
        • short term (<24 hrs) 3.4-26.6% down
        • long term (>24 hrs) 11.9-65% down
      • Resistance exercise
        • short term (<24 hrs) 30% down
        • long term (>24 hrs) 35% down
    • The most consistent benefits were seen in long-duration (≥ 45 min), moderate-intensity aerobic exercise
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    Added June 5 2024:
    2009 May: The Correlation of Hemoglobin A1c to Blood Glucose
    • Hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes.
    • Even as complex as human blood is, it seems as though HbA1c correlates to any single glucose measurement.
    • Several studies have shown that CGM glucose averages account for the vast proportion of the variation of HbA1c.
    • A regression equation was developed (average glucoseCGM = 31.5 × HbA1c - 68.6). For example: If the target HbA1c is 5.4, then the formulat would be avgCGM = (31.5 * 5.4) - 68.6 or avgCGM = 101.5 mg/dL.
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    Added November 19 2024:
    2021 Nov.: Association of changes in lipid levels with changes in vitamin D levels in a real‑world setting
    • Hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes.
    • Even as complex as human blood is, it seems as though HbA1c correlates to any single glucose measurement.
    • Several studies have shown that CGM glucose averages account for the vast proportion of the variation of HbA1c.
    • A regression equation was developed (average glucoseCGM = 31.5 × HbA1c - 68.6). For example: If the target HbA1c is 5.4, then the formulat would be avgCGM = (31.5 * 5.4) - 68.6 or avgCGM = 101.5.
  20. Top
    Added December 1, 2024:
    2024 Oct.; Cancer Care The Role of Repurposed Drugs and Metabolic Interventions In Treating Cancer 2nd Edition
    • This is a PDF download
    • Chapter 1: Introduction
    • Chapter 2: What is cancer: understanding its pathogenetic causes
    • Chapter 3: Preventing cancer
    • Chapter 4: The metabolic approach to treating cancer
      • Glucose management and the ketogenic diet
    • Chapter 5: Metabolic and lifestyle interventions for cancer treatment
    • Chapter 6: Repurposed drugs
    • Chapter 7: Tier one repurposed drugs – strong recommendation
    • Chapter 8: Tier two repurposed drugs – weak recommendation
    • Chapter 9: Tier three repurposed drugs -insuficient data
    • Chapter 10: Tier four repurposed drugs – recommend against
    • Chapter 11: Potential adjunctive therapies
    • Chapter 12: Chemotherapy: a basic primer
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    Added December 2, 2024:
    2011 26 Oct.; Is there a role for carbohydrate restriction in the treatment and prevention of cancer?
    • Most, if not all, tumor cells have a high demand on glucose compared to benign cells of the same tissue and conduct glycolysis even in the presence of oxygen (the Warburg effect).
    • Many cancer cells express insulin receptors (IRs) and show hyperactivation of the IGF1R-IR pathway.
    • Evidence exists that chronically elevated blood glucose, insulin and IGF1 levels facilitate tumorigenesis and worsen the outcome in cancer patients.
    • CHO restriction mimics the metabolic state of calorie restriction or - in the case of KDs - fasting. The beneficial effects of calorie restriction and fasting on cancer risk and progression are well established.
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    Added December 2, 2024:
    2024 22 July; Effects of protein restriction on insulin-like growth factor (IGF)-1 in men with prostate cancer: results from a randomized clinical trial
    • These findings demonstrate that protein restriction without calorie restriction does not reduce serum IGF-1 concentration or increase IGFBP-1 and IGFBP-3 in men with localized prostate cancer.
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    Added December 2, 2024:
    2024 16 Feb.; High-fat diet promotes prostate cancer metastasis via RPS27
    • Our findings indicate that HFD increases the risk of PCa metastasis by elevating RPS27 expression and, subsequently, the expression of genes involved in PRAD progression.
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    Added December 2, 2024:
    2018 Aug 1.; Mechanisms of Insulin Action and Insulin Resistance
    • Paper divided into VIII (8) sections.
      1. Introduction
      2. The effectors and effects of direct, cell-autonomous insulin action in muscle, liver, and white adipose tissue are reviewed, beginning at the insulin receptor and working downstream.
      3. Considers the critical and underappreciated role of tissue crosstalk in whole body insulin action, especially the essential interaction between adipose lipolysis and hepatic gluconeogenesis.
      4. The pathophysiology of insulin resistance is described. Special attention is given to which signaling pathways and functions become insulin resistant in the setting of chronic overnutrition, and an alternative explanation for the phenomenon of ‟selective hepatic insulin resistanceˮ is presented.
      5. Reviews work linking the bioactive lipids diacylglycerol, ceramide, and acylcarnitine to insulin resistance.
      6. Considers the impact of nutrient stresses in the endoplasmic reticulum and mitochondria on insulin resistance.
      7. Discusses non-cell autonomous factors proposed to induce insulin resistance, including inflammatory mediators, branched-chain amino acids, adipokines, and hepatokines.
      8. We propose an integrated model of insulin resistance that links these mediators to final common pathways of metabolite-driven gluconeogenesis and ectopic lipid accumulation.
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    Added December 3, 2024:
    2007 July 01 .; Prospective Study of Type 1 and Type 2 Diabetes and Risk of Stroke Subtypes: The Nurses’ Health Study
    • Both type 1 and type 2 diabetes are associated with substantially increased risks of total and most subtypes of stroke.
    • A higher incidence of stroke subtypes among those with type 1 diabetes could be attributable to younger age at onset, longer duration of diabetes, insulin deficiencyInsulin deficiency is defined as a pathological condition in which there is an inappropriate decrease in the rate at which the (3-cell secretes insulin. , and development of hypertension with diabetic nephropathy, disturbances of coagulation-fibrinolytic parameters, increased platelet adhesiveness, or episodes of hypoglycemia.
    • To decrease the risk of stroke associated with diabetes, treatment of underlying glycemia, hypertension, dyslipidemia, and platelet aggregation must all be considered.
    • Our findings of an excess of lacunar infarctsA lacunar infarct is a small, deep brain stroke that occurs due to the occlusion of a single penetrating artery, typically stemming from the larger cerebral arteries, and is considered a hallmark of cerebral small vessel disease (CSVD), often strongly linked to uncontrolled hypertension in women with diabetes have been observed in other studies
    • Diabetes can cause small-vessel arteriolopathy, especially in the retina, kidney, and deep structures in the brain Fisher CM: Lacunar infarcts: a review. Cerebrovasc Dis1 :311 –320, 1991
    • No reference to glucose in this article.
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    Added December 7, 2024:
    Unknown date; What happens when you don’t eat any carbs?
    • This is not a research paper, any references to back up the SPOAFing are, self-admittedly weak, ungraded, and sometime contradictory to the beginning statement (next list item).
    • Statement at the beginning of the article: "What happens if you eat far fewer than 110 grams of carbs per day, or even no carbs at all? Does the brain starve? Absolutely not!"
    • Statement at the end of the article: "It’s true that the brain can’t run entirely on ketones; it needs some glucose as well."
    • Statements between:

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