Research Regarding Glucose Management
Diabetes and Other IssuesReturn
Cholesterol
Cholesterol is typically split into three categories
UTH-1
High-density lipoprotein (HDL)HDL (good cholesterol): Helps remove excess cholesterol from the bloodstream
Low-density lipoprotein (LDL)LDL (bad cholesterol): Can build up in arteries and increase the risk of heart disease.
Very low-density lipoprotein (VLDL)VLDL: Also considered "bad" cholesterol, primarily carries triglycerides
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.
Thrombin generation and fibrin clot structure after vitamin D supplementation
In severe vitamin D deficiency, a high-dose cholecalciferol supplementation was associated with a reduction in thrombin generation and an average decreased number of fibrin protofibrils per fibers and fibrin fiber size measured by turbidimetry. This suggests that severe vitamin D deficiency may be associated with a potentially reversible prothrombotic profile.
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 Return
1 Study finds that 93% of normal (non-diabetic) people reach IGTImpaired Glucose Tolerance is a condition where your blood sugar levels are higher than normal, but not high enough to be diagnosed as diabetes: at least once per day
2 By 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
3 Two portions of cheeses/day reduced the risk of having high blood glucose levels by approximately 80%
4 A 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
5 Metformin Should Not Be Used to Treat Prediabetes
6 Metformin Should Be Used to Treat Prediabetes
7 Supplementation of Vitamin C Reduces Blood Glucose
8 Appendis AFDA safety announcements for metformin
9 Lower Time In Range (TIR) equates to higher morbidity
10 Observational study of the efficacy of prolonged-release metformin in people with prediabetes
11 Metformin use in prediabetes: is earlier intervention better?
12 Exercise may limit the effectiveness of metformin
13 An overview of how metformin works
14 Metformin shown to have anti-cancer properties
15 Metformin and Prostate Cancer: a New Role for an Old Drug
16 The timing of physical activity after eating, and the effect on glucose
17 Physical activity can reduce the duration and size of the glucose spike after eating.
18 The Correlation of Hemoglobin A1c to Blood Glucose
19 Association of changes in lipid levels with changes in vitamin D levels in a real‑world setting
20 Glucose management and the ketogenic diet.
21 Carbohydrate gGlucose management and cancer.
22 Effects of protein restriction on insulin-like growth factor (IGF)-1 in men with prostate cancer
23 HFD (High Fat Diet) increases the risk of PCa metastasis
Comments & Notes Return
Freestyle Libre Glucose MonitorFSM-1
I installed mine on May 16, 2024 at 12:28 PM.
Stopped using it on Jun 26, 2024
Glucose Monitor WatchGMW-1
My glucose levelGMW-2
My glucose level with notationGMW-3
My cholesterol levelsGMW-3
Insulin Response or Resistance Return
After watching my CGMContinuous Glucose Monitoring reports typically display glucose levels in units of mg/dL (milligrams per deciliter) in the United States, while internationally, the unit used is mmol/L (millimoles per liter). GMW-1 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 EkbergReturn
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)
Lower insulin
Stop eating sugar
Reduce carbs
Eat fewer meals
Gentle exercise
Use fat > glucose
Glucose > fat => Cravings
Abbreviations and AcronymsReturn
ADAG A1C-Derived Average Glucose
CGM Continuous interstitial Glucose Monitoring
FPG Fasting Plasma Glucose
IGT Impaired Glucose Tolerance
IQR InterQuartile Range
OGTT Oral Glucose Tolerance Test
References:
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Added May 17 2024:
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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:
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:
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 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:
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 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.
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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:
2018 Aug 1.; Mechanisms of Insulin Action and Insulin Resistance
Paper divided into VIII (8) sections.
Introduction
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.
Considers the critical and underappreciated role of tissue crosstalk in whole body insulin action, especially the essential interaction between adipose lipolysis and hepatic gluconeogenesis.
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.
Reviews work linking the bioactive lipids diacylglycerol, ceramide, and acylcarnitine to insulin resistance.
Considers the impact of nutrient stresses in the endoplasmic reticulum and mitochondria on insulin resistance.
Discusses non-cell autonomous factors proposed to induce insulin resistance, including inflammatory mediators, branched-chain amino acids, adipokines, and hepatokines.
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:
Drug Half-Life CalculatorReturn
Following is a Half-Life Calculator where you can enter your calculated dose (from above). Enter the half-life of Ivermectin (18 hours). Enter how often you wish to take the dose (agressive = every 24 hours, prophylactic = 168 hours).
Global input
Half-life: hours
If taken regularly
Time between doses: hours
Stabilized daily min–max (sum of residuals):
– mg
( – x)
To ramp up to maximum level (within the percentage above):
doses ( )
Ramp up details
To ramp back down from maximum (within the percentage above):
hours
( days)
If taken once
Time for one isolated dose to drop within the percentage above:
hours
( days)
Level after 24 hours, for one isolated dose: mg