Pete is a 55-year-old man who comes to you with complaints of increased thirst, a 10-lb weight loss, and fatigue. You last saw him 18 months ago, when you told him he had pre-diabetes. At that time, his HbA1c was 5.9l%; fasting blood sugar, 111 mg/dL; triglycerides, 187 mg/dL; and HDL, 38 mg/dL. You advised lifestyle changes.
Since his last visit, Pete gained 22 lb; he then began to lose weight. His “diet” lasted 3 weeks. His lab values at this visit are: HbA1c, 10.4%; random blood sugar, 455 mg/dL; total cholesterol,180 mg/dL; non-HDL, 149 mg/dL; LDL, 78 mg/dL; triglycerides, 355 mg/dL; HDL, 31 mg/dL.
Pete has no signs of cardiovascular disease, nephropathy, or other indicators of diabetes complications. He has reasonable insurance coverage, is literate, and has the other resources needed for adequate diabetes care.
Oral medication will probably not be effective for a patient with such a high blood sugar level and HbA1c. The glucotoxicity created by the high blood glucose level and lipotoxicity created by the high level of circulating free fatty acids have stunned the pancreas and limited its ability to respond.
Intensive insulin is the most appropriate choice. The insulin may only be needed for a short period (2 to 3 weeks) to bring the blood sugar to normal levels. Some authors believe that the timing of the intervention affects the metabolic response to insulin therapy. Beta cells that are are exposed to chronic hyperglycemia eventually decompensate. Early aggressive physiologic insulin replacement with both prandial and basal coverage results in rapid improvement in glucolipotoxicity, reduction of the inflammatory milieu, and consequent greater preservation of beta-cell function or recovery of beta-cell function.1 This theory was proven by 3 studies2-4 that employed intensive insulin therapy through multiple daily insulin injections, or insulin pump over a 2- to 3-week period. In these studies, 90% of patients achieved euglycemia at the end of the 2- to 3-week period and the insulin was stopped. After insulin cessation, 42% to 69% of the patients maintained euglycemia for 12 or more months with diet therapy only.
These studies seem to prove the point about beta-cell decompensation and recovery and provide evidence for considering early intensive insulin treatment in patients with newly diagnosed diabetes.
Pete most likely has type 2 diabetes, but a late-onset type 1 is possible. Type 1 disease will not be controlled once the insulin is stopped. I would use insulin for 3 weeks or until the patient is euglycemic and then see whether lifestyle alone is effective. If it is not, I would add metformin(Drug information on metformin) and then consider a GLP-1 agonist.
I would also start statin therapy. This patient’s LDL level is low, but it is a calculated LDL. Once the blood sugar level is normalized, the hypertriglyceridemia and low HDL level will improve. His LDL level will also increase. The non-HDL is a better target (100 to 130 mg/dL) than his LDL.5 If the triglycerides and HDL do not return to normal levels after treatment with a statin, lifestyle changes, and insulin, then other medications (eg, fibrates or niacin) may be appropriate.
1. Meneghini L. Early insulin treatment in type 2 diabetes. What are the pros? Diabetes Care. 2009;32(suppl 2):S266-S269.
2. Li Y, Xu W, Liao Z, et al. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients is associated with improvement of beta-cell function. Diabetes Care. 2004;27:2597-2602.
3. Ilkova H, Glaser B, Tunckale A, et al. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment. Diabetes Care. 1997;20:1353-1356.
4. Ryan EA, Imes S, Wallace C. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes. Diabetes Care. 2004;27:1028-1032.
5. Boekholdt SM, Arsenault BJ, Mora S, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012;307:1302-1309.