Physicians should adopt a precision medicine approach to type 2 diabetes by identifying the specific phenotype of each patient, rather than treating it as a single, uniform disease, to provide optimal care.
Consider starting combination therapy for type 2 diabetes from the outset, as recommended by the American Diabetes Association, rather than a stepwise approach, to address the multiple underlying pathophysiological defects.
For optimal type 2 diabetes treatment, if cost is not a barrier, prioritize a newer GLP-1 agonist as a foundational drug, add pioglitazone for insulin sensitization, and an SGLT2 inhibitor as a third, especially if there is renal or cardiac disease.
For effective type 2 diabetes management, consider a triple therapy approach using older, affordable drugs like metformin, exenatide (an older GLP-1 agonist), and pioglitazone, as this combination has shown significant improvements in A1C, insulin sensitivity, and beta cell function.
Consider pioglitazone (Actos) as a true insulin sensitizer to correct insulin signaling defects and redistribute fat from organs like muscle, liver, and beta cells to subcutaneous tissue, improving overall metabolic health.
Consider using SGLT2 inhibitors in newly diagnosed diabetics without existing cardiac symptoms for primary prevention of cardiovascular and renal disease, based on their documented benefits in secondary prevention.
Recognize that GLP-1 agonists are powerful for improving and preserving beta cell function in type 2 diabetes, not just for weight loss, and this effect is crucial for long-term disease management.
If you have type 2 diabetes and are taking high doses of insulin (e.g., 75 units/day), aim to reduce it to a more physiological level (around 35 units/day) through nutrition, exercise, and other pharmacological interventions.
Avoid chronic hyperinsulinemia, as it can down-regulate the insulin signaling system and induce insulin resistance, making the condition worse.
Implement lifestyle changes such as weight loss and exercise, alongside appropriate medications (insulin sensitizers or weight-loss drugs), to effectively reduce insulin dosage in individuals with type 2 diabetes.
Recognize childhood obesity as a critical public health concern leading to early-onset, aggressive type 2 diabetes that is often resistant to conventional treatments, necessitating early and aggressive intervention strategies.
Address the obesity epidemic by tackling multiple contributing factors, including processed and calorically dense foods, lack of exercise, and the resulting changes in brain neurocircuitry related to food intake.
Pay close attention to the one-hour glucose level during an Oral Glucose Tolerance Test (OGTT); a reading greater than 155 mg/dL is a strong predictor of developing type 2 diabetes, regardless of other metrics.
If an OGTT shows a high insulin response at 30 minutes followed by hypoglycemia at two hours, it indicates a pre-diabetic state with significant insulin resistance and an overshooting beta cell response.
A low insulin response at 30 minutes during an OGTT, indicating a loss of first-phase insulin secretion, is a predictor of a primary beta cell defect and future type 2 diabetes development.
To accurately assess insulin secretion, measure C-peptide levels rather than insulin levels, as C-peptide is not taken up by the liver and thus provides a more reliable measure of pancreatic beta cell output.
When discussing or assessing insulin resistance, specify the affected tissue (e.g., muscle, liver, fat cell, brain) and the particular metabolic process, as insulin’s actions vary across tissues.
Do not be deterred by weight gain when using pioglitazone, as studies show that greater weight gain with this drug correlates with improved A1C, insulin sensitivity, beta cell function, blood pressure, triglycerides, and HDL cholesterol due to fat redistribution.
Consider pioglitazone (Actos) as the best drug for treating Non-Alcoholic Steatohepatitis (NASH) due to its fat redistribution effects.
Recognize that pioglitazone has demonstrated cardiovascular safety and benefit, with weight gain on the drug paradoxically correlating with reduced mortality in the PROactive study.
Utilize metformin as a cost-effective foundational drug in combination therapy for type 2 diabetes, as it is inexpensive and can be safely added to other medications.
Understand that metformin primarily reduces hepatic glucose output by inhibiting gluconeogenesis and does not directly improve insulin sensitivity in muscle, as it cannot enter muscle cells.
When prescribing powerful new drugs like GLP-1 agonists for severe type 2 diabetes, ensure patient adherence, affordability, and proper medical guidance, as these factors are critical for sustained success and preventing relapse.
Listen to this podcast episode with Dr. Ralph DeFranzo multiple times to fully grasp the complex information on type 2 diabetes and insulin resistance.
Listen to Peter Attia’s previous podcast episode with Jerry Shulman to understand insulin resistance, particularly its manifestation in muscle.
For precise assessment of beta cell function in a research or specialized clinical setting, consider advanced techniques like a three-step hyperglycemic clamp followed by sequential infusions of GLP-1 and amino acids to measure specific responses to different stimuli.
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