Case Study: A 64-Year-Old Man With a 9-Year History of Type 2 Diabetes in Whom Insulin Therapy Led to Improved Control But No Weight Gain After 6 Months

L.T. is a 64-year-old white man with a 9-year history of type 2 diabetes. He suffered an inferior wall myocardial infarct 2 years ago. He also has a 7-year history of hypertriglyceridemia and hypercholesterolemia, as well as gout and abdominal obesity. He has no history of cigarette smoking.

At his initial visit to the endocrinology clinic, his weight was 242 lb., and he was 70 inches tall. Thus, his BMI was 35 kg/m². His blood pressure was 130/78 mmHg, and his hemoglobin A_1c (A1C) result was 9.0% (normal: 4.3–6.1%) on 2,000 mg/day of metformin and 10 mg/day of glyburide. A lipid panel revealed fasting serum triglycerides of 288 mg/dl, total cholesterol of 160 mg/dl, HDL cholesterol of 36 mg/dl, and LDL cholesterol of 66 mg/dl. His fasting blood glucose level was 331 mg/dl. In addition to metformin and glyburide, medications included simvastatin, 10 mg/day; niacin,750 mg twice daily; allopurinal, 300 mg/day; and aspirin, 325 mg/day.

L.T.’s primary care provider had been reluctant to start him on insulin, even though he was taking close-to-maximal doses of oral hypoglycemic agents without achieving acceptable diabetes control. The provider worried that, once L.T. started on insulin, he would regain the 20 lb. he had lost since his myocardial infarct and that the negative impact of this weight gain would outweigh the positive impact of enhanced diabetes control on his overall health. Taking these concerns into account, the endocrinologist started L.T. on 10 units/day of glargine at bedtime, to be taken in addition to his regimen of metformin and glyburide.

L.T. and his wife then scheduled an appointment for medical nutrition therapy (MNT) with a registered dietitian who was a certified diabetes educator. L.T.’s 3-day food record showed excessive calorie intake with > 90–120 g of carbohydrate per meal. The dietitian taught the couple carbohydrate counting and fat modifications and encouraged them to keep food intake and self-monitoring of blood glucose (SMBG) records. The dietitian also recommended an individualized exercise program.

In the course of the next 6 months, L.T. saw the dietitian two times for reviews of the nutrition and exercise therapy and SMBG records. At these visits, patient food records were assessed for carbohydrate and fat as well as calorie intake. These records along with SMBG records and laboratory results served as a springboard for teaching the effect of the food plan on blood glucose results and lipids.

During that period, the patient’s intake was approximately 1,500–1,800 kcal/day, with 60–75 g of carbohydrate/meal, and < 30% of total energy from fat. Foods with lower saturated fat content were emphasized. The patient was riding a stationary bicycle for 1 hour/day. After discussing patient preferences, the dietitian suggested gradually increasing exercise by adding a walk 3–4 times/week.

Throughout the course of MNT, the dietitian titrated L.T.’s insulin dose weekly via telephone, working under a protocol approved by the endocrinologist to achieve a fasting blood glucose level ≥ 80–100 mg/dl. L.T. experienced no hypoglycemia during this time.

After 6 months, L.T. had achieved an A1C of 7% on 14 units of glargine and his usual doses of metformin and glyburide. His weight was 234 lb. (a decrease of 8 lb.), his serum triglyceride level was 179 mg/dl (a decrease of 38%), and his HDL cholesterol was 39 mg/dl (an increase of 3 mg/dl). His blood pressure was 120/74 mmHg. Thus, he was able to lose 3% of his body weight while initiating insulin therapy and tightening glycemic control. In addition, both the patient and his wife commented on how significantly improved his mood and energy level were with more normalized blood glucose levels.

L.T. had tried unsuccessfully after his heart attack to lose weight and control his blood glucose. The addition of glargine with subsequent lowering of his blood glucose gave him hope and motivation to once again try to lower his weight. Once he saw the difference he could make in his blood glucose levels, he began exercising and following a healthy meal plan again in earnest.

1. Do all patients starting on insulin gain weight? How much weight gain is to be expected?

2. How would one optimize chances to limit weight gain or assist a patient in maintaining or even losing weight?

3. If this patient had gained weight instead of lost weight, would he have increased his risk of cardiovascular disease even though he dramatically improved his glycemic control?

There is ample evidence in the literature to support the primary care provider’s concern about L.T.’s potential weight gain. Weight gain is commonly seen when patients are started on insulin. A recent quantification of this weight gain in patients with type 2 diabetes showed that it is modest; mean weight gain on a regimen of twice daily insulin was 3.3 kg during the first 6 months and 1.3 kg over the second 6 months.1 Patients in the U.K. Prospective Diabetes Study (UKPDS) randomized to intensive control with sulfonylureas or insulin gained more weight than did those randomized to diet therapy alone. Patients treated with insulin gained about 4 kg, whereas those on chlorpropamide or glyburide gained 2.6 or 1.7 kg, respectively.2 Additionally, the UKPDS showed that weight gain is also associated with treatment to lower blood pressure, particularly with β-blocker therapy.

Given that 90% of patients with type 2 diabetes are obese, additional weight gain is certainly a concern. Obesity is related to most cardiovascular risk factors and has been shown to induce multiple risk factors of cardiovascular disease. Obesity substantially increases the prevalence of arterial hypertension. It also increases the prevalence of dyslipidemia, is a major risk factor in the development of congestive heart failure, and induces left-ventricular hypertrophy. Lastly, obesity is an independent risk factor for cardiovascular disease, particularly sudden cardiac death.3 Obesity also appears to be an independent risk factor for two complications of type 2 diabetes. In the UKPDS, for every 0.1 unit increase in the waist-to-hip ratio, there was an increase of 15% in the risk for microalbuminuria. Patients with microabluminuria are at increased risk of nephropathy and cardiovascular disease.4 

However, there is also ample evidence to support the intensive treatment of hyperglycemia, even in, or perhaps especially in, patients with cardiovascular disease. Epidemiological studies have shown a link between severity of hyperglycemia and risk for cardiovascular disease.1 The DIGAMI study5 hinted that insulin may reduce the risk of cardiovascular disease in people with type 2 diabetes. And in the UKPDS, treatment of hyperglycemia and hypertension reduced the risk of diabetes complications. In particular, reducing a patient’s A1C from 7.9 to 7.0% was associated with a 16% drop in risk of myocardial infarct (P = 0.052).2 The intensive treatment of hyperglycemia with insulin serves to improve dyslipidemia even when a modest amount of weight is gained. In addition, quality-of-life issues are highly pertinent. Hyperglycemia induces fatigue, irritability, and depression in levels equivalent to an A1C of 9%.6 

Different systems of MNT and different pharmaceutical regimens have been studied in an attempt to limit weight gain upon insulin initiation. Because this weight gain is seen to be caused by the retention of calories as glycosuria is decreased, advice on nutrition and exercise seems wise. MNT as performed by registered dietitians resulted in less weight gain at 6 months (1.3 vs. 3.3 kg) when therapy was intensified to improve glycemic control in a group of patients with type 2 diabetes.7 Patients who received MNT experienced no increase in waist-to-hip ratio and, therefore, no increased risk of cardiovascular disease as a result of this minimal weight gain. The addition of NPH insulin to an existing regimen of oral antidiabetic agents has been shown to induce less weight gain than does a two-injection insulin regimen only.8 In addition, glargine used once daily at bedtime results in significantly less weight gain than does NPH insulin.9 

Because we now know that type 2 diabetes is a progressive disease and that pancreatic β-cell function deteriorates over time, eventually initiating insulin in type 2 diabetes has become a given. Insulin will prevent significant hyperglycemia and reductions in quality of life. Not all patients starting insulin will gain weight. For those who do, weight gain can be lessened with MNT and the use of newer insulin regimens. The UKPDS and other studies have shown that, for patients with preexisting cardiovascular disease, initiating insulin and tightening glycemic control can significantly reduce the risk of cardiovascular disease despite possible modest weight gains. Thus, potential weight gain is not a viable reason for avoiding insulin therapy.

• Fear of weight gain is not a valid reason to avoid intensive treatment of hyperglycemia with insulin therapy.

• The therapeutic impact of improved glycemic control trumps the potential modest weight gain resulting from initiation of insulin in patients with type 2 diabetes.

• MNT and newer insulins can help to minimize or prevent weight gain when initiating insulin therapy in type 2 diabetic patients.