Weight gain in type 2 diabetes mellitus—Not all uphill

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Abstract

Objective

The goal of this study, of type 2 diabetes mellitus patients, treated in a referral community setting, was to follow the history of weight changes, in relation to the changing treatment modalities, and to detect independent risk factor and predictors for weight gain.

Research Methods

366 outpatients with type 2 diabetes (T2DM) were followed longitudinally for at least 5 years. 310 patients were treated with oral hypoglycemic agents and 56 patients had insulin treatment added to the oral therapy.

Results

The two groups did no differ significantly in the duration of diabetes, age of onset and admission HbA1c. The mean weight at admission was 78.9 ± 15.1 and 76.7 ± 15.0 kg (ns) respectively. No significant weight changes were noted on initiation of oral treatment and at final visit. The commencing of insulin therapy was the only step associated with a significant 3.7 kg increase in body weight (p < 0.001) with a significant reduction in HbA1c (−1.4%, p < 0.001). These changes however, followed a decrease in body weight that preceded insulin therapy. Mean weight at follow-up did not exceed the self-reported weight prior to the diagnosis of diabetes.

Discussion

The results show that weight gain does not necessarily accompany treatment of T2DM. Insulin therapy in T2DM is associated with some weight gain, mostly due to correction of glycemia and improvement of weight loss prior to insulin treatment. This should encourage the timely addition and combining of appropriate therapeutic modalities in order to achieve good glycemic control.

Introduction

Weight gain traditionally accompanied the treatment of type 2 diabetes. The UKPDS study [1] was seminal in showing the different effects of therapeutic modalities on weight gain. The UKPDS data were similar to other, previous studies, demonstrating that all treatment modalities including diet and metformin were associated with weight increase, but that insulin and SU therapy caused the greatest increase in weight [1], [2]. Underlying mechanism for the observed weight increase during reduction of HbA1c is multifactorial—all treatment modalities cause preservation of calories due to decrease in glucosuria, but the reason for the divergent effects of the different treatment options on weight is still unclear. Metformin reduces food intake and hypoglycemic episodes – factors associated with weight gain and thus is the preferred drug for the obese diabetic patients. Increase in hypoglycemia rate associated with insulin and SU – leading to increase in food intake, might partially explain the weight gain induced by these drugs. Other, mechanisms such as a decrease in metabolic rate induced by insulin therapy might theoretically add to its weight gain effect [2], [3].

While weight gain during clinical trials was typically the rule, averaging in 2–5 kg increase on oral therapy and over 8 kg with insulin [7], [8], [9], emerging data from real world populations has shown conflicting results. Either no weight gain or smaller weight changes than those previously reported in clinical trials were reported in registries following patients from 1 to 12 years [10], [11], [15]. Data from the Pima Indians, going back up to 20 years prior to the onset of diabetes, actually showed a reduction of weight with the different treatment modalities [12].

Therefore, our objective was aimed at assessing weight gain in diabetic patients receiving standard medical care in a community based diabetic clinic. The advantage of the clinic is in the stable population it served and that clinical data was collected prospectively for 20 years. The treatment policy was also unvarying, following a stepped care approach of medical nutritional therapy (MNT) followed by oral treatment (metformin and sulfonylureas) and addition of insulin if oral therapy failed to reach glycemic goals of HbA1c < 8.0%. The thiazoladinedione class of medication was not widely used at the period of the study. Insulin was usually initiated in combination with oral therapy. We hypothesized, based on our clinical observations, that most patients following this therapeutic scheme do not increase their weight above pre-diabetic levels and that only a minority of patients had a significant (>10 kg) increase in weight gain. Our secondary goal was to characterize and predict those who gain excessive weight during treatment.

Section snippets

Study population

The study group included all type 2 diabetic patients seen at the regional diabetic outpatient clinic from January 1985 through December 2000. The clinic serves most of the diabetic patients in a community with an urban population of 150,000. All the data were prospectively compiled on relational databases. Data included 5500 medical records with demographic and clinical information on arrival, updated every 3–6 months.

Patients fulfilled the following inclusion criteria. (1) Followed regularly

Demographics

Patient characteristics are shown in Table 1. Age at referral was 68.6 ± 10.0 years with mean duration of diabetes 14.1 ± 6.6 years. 58% were male. The patients subjective self-reported weight before the diagnosis of diabetes was 83.4 ± 15.9 kg. Weight at admission was 78.6 ± 15.1 kg with a BMI of 29.4 ± 5.0 kg/m2. There were several significant differences between the two groups: Though the age at referral was similar, the age of onset of diabetes in the ins group was younger and therefore the duration of

Discussion

This study analyzed the course of weight gain, during more than 7 years of treatment of type 2 diabetes, as the treatment progressed from MNT to oral agents and following the addition of insulin. The average weight (and BMI) did not increase significantly during the transition to oral treatment in the two groups (treated and not treated with insulin). But, when patients initiated insulin therapy, a significant 3.5 kg increase in weight was observed. The increase in weight paralleled a reduction

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