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Prediabetes Glucose Management

Quick Summaries

• ¹Study finds that 93% of normal (non-diabetic) people reach IGT at least once per day
• ²By assessing across age groups in a healthy, nondiabetic population, normative sensor glucose data have been derived and will be useful as a benchmark for future research studies
• ³Two portions of cheeses/day reduced the risk of having high blood glucose levels by approximately 80%
• ⁴A random venous blood glucose of at or above 11.1 mmol/L (≥200 mg/dL) or a fasting blood glucose at or above 7 mmol/L (≥126 mg/dL) on two or more separate occasions indicates the client is likely to have diabetes mellitus
• ⁵Metformin Should Not Be Used to Treat Prediabetes
• ⁶Metformin Should Be Used to Treat Prediabetes
• ⁷Supplementation of Vitamin C Reduces Blood Glucose
• ⁸Appendis AFDA safety announcements for metformin
• ⁹Lower Time In Range (TIR) equates to higher morbidity
• ¹⁰Observational study of the efficacy of prolonged-release metformin in people with prediabetes
• ¹¹Metformin use in prediabetes: is earlier intervention better?
• ¹²Exercise may limit the effectiveness of metformin
• ¹³An overview of how metformin works
• ¹⁴Metformin shown to have anti-cancer properties
• ¹⁵Metformin and Prostate Cancer: a New Role for an Old Drug
• ¹⁶The timing of physical activity after eating, and the effect on glucose
• ¹⁷Physical activity can reduce the duration and size of the glucose spike after eating.

Comments & Notes

Freestyle Libre Glucose Monitor^FSM-1

I installed mine on May 16, 2024 at 12:28 PM.




Insulin Response or Resistance

After watching my CGM numbers bounce around, I found myself asking: In an individual, is there a way to tell if glucose regulation is being affected more by slow insulin production response or higher resistance to the insulin being produced?

There is no easy answer, because there is no single test that will expose either situation.

However, there are a combination of tests and observations that may provide a some insight:

• Blood Tests:
• Fasting Plasma Glucose (FPG)^{1, 5, 10, 11}

Although it doesn't differentiate between insulin production or insulin resistance, this test measures blood sugar levels after not eating for at least 8 to 16 hours. A higher than normal FPG can indicate impaired fasting glucose (IFG)⁴ or even diabetes..

• Hemoglobin A1c (HbA1c):^{1, 5, 9}

This test reflects average blood sugar control over the past 2-3 months. While not a diagnostic tool on its own, a high HbA1c suggests chronic hyperglycemia (high blood sugar).

• Insulin Levels:

Measuring fasting or stimulated insulin levels can provide some insight. Lower than normal fasting insulin might suggest insufficient production, while high insulin levels with high blood sugar could indicate resistance.

• Other Observations:
• Age:

Type 1 diabetes typically develops in childhood or young adulthood, often due to an autoimmune attack on insulin-producing cells. Type 2 diabetes is more common in adults and can be linked to factors like obesity and family history, which are more indicative of insulin resistance.

• Body Composition:

Excess weight, particularly around the waist, is a strong risk factor for insulin resistance.

• Further Tests:
• Oral Glucose Tolerance Test (OGTT):

This measures blood sugar levels after a sugary drink. The rise and fall of blood sugar can provide clues about insulin production and sensitivity.

• C-Peptide Test:

C-peptide, also called a connecting peptide, connects two important molecules:

• Alpha chain:

This is one of the two polypeptide chains that form mature insulin.

• Beta chain:

This is the other polypeptide chain that forms mature insulin.

• Here's a breakdown of the process:
• Proinsulin Synthesis: Within the pancreas, specialized beta cells in the islets of Langerhans synthesize a larger molecule called proinsulin. Proinsulin is an inactive precursor to insulin.
• C-peptide Bridge: Proinsulin consists of three polypeptide chains: alpha chain, beta chain, and a connecting chain called C-peptide. The C-peptide acts as a bridge, linking the alpha and beta chains together.
• Cleavage and Release: Enzymes within the pancreas cleave proinsulin at specific sites, separating the C-peptide from the alpha and beta chains. The mature insulin molecule (formed by the linked alpha and beta chains) and the free C-peptide are then packaged into secretory vesicles within the beta cells.
• Secretion: When blood sugar levels rise, the beta cells are triggered to release both insulin and C-peptide into the bloodstream.
• Why is C-peptide Important?
Insulin Action: Mature insulin is the key player here. It travels through the bloodstream and binds to receptors on cells, allowing glucose (sugar) to enter the cells for energy production. C-peptide as a Byproduct: C-peptide itself doesn't have a direct effect on blood sugar levels. However, because it's released in equal amounts alongside insulin, it can be a helpful marker for the body's insulin production capacity.



By combining these tests and observations, doctors can develop a more nuanced understanding of the underlying cause of impaired glucose regulation. In some cases, both slow insulin production and high insulin resistance might be contributing factors. Treatment will then be tailored to address the specific issues at play.

Notes from Dr. Sten Ekberg

• Youtube: #1 Absolute Best Way To Lower Blood Sugar
  • About a 28 minute video
  • At about the 2:50 point he talks about "normal" vs "opitmal"

  	Fasting	30 min. after eating	2 to 3 hours after eating
  normal	70 - 100	170 - 200	120 - 140
  Impaired	101 - 125	190 - 230	140 - 160
  T2D	126+	220 - 300	200+
  Optimal	80 - 90	90 - 110	80 - 90

• How To Lower Blood Sugar (process explained in youtube)
1. Lower insulin
2. Stop eating sugar
• 50/50 Glucose + sugar
3. Reduce carbs
• All carbs => sugar
4. Eat fewer meals
• No food = no insulin
5. Gentle exercise
• Use fat > glucose
• Glucose > fat => Cravings

Example Search Arguments

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• site:nih.gov normal glucose level non diabetic
• site:nih.gov metformin prostate

Abbreviations

References:

1. ^{Top Back}

   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.

2. ^{Top Back}

   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.

3. ^{Top Back}

   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).

4. ^{Top Back}

   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
5. ^{Top Back}

   Added May 19 2024:

   2020 Sep.:Metformin Should Not Be Used to Treat Prediabetes

   • About the author: Mayer B. Davidson

   • 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.
6. ^{Top Back}

   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.
7. ^{Top Back}

   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
8. ^{Top Back}

   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
9. ^{Top Back}

   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%.
10. ^{Top Back}

    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
11. ^{Top Back}

    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.
12. ^{Top Back}

    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.
13. ^{Top Back}

    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.
14. ^{Top Back}

    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 Back}

    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].
16. ^{Top Back}

    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 Back}

    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
18. ^{Top Back}

    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.