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Prediabetes Glucose Management

Quick Summaries

Comments & Notes

Notes from Dr. Sten Ekberg

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


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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:
    • 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].
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    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.
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    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.



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