Type 2 diabetes with partial lipodystrophy of the limbs: a new lipodystrophy phenotype

Abstract

Objective: Lipodystrophies are categorized by the extent of fat loss (generalized vs. partial) and by inheritance (congenital vs. acquired). We examined whether a group of patients with partial lipodystrophy of the limbs (PLL), type 2 diabetes mellitus (T2DM), and an absence of a family history of lipodystrophy constitute a new clinical subtype.

Research design and methods: Ten women with T2DM and PLL were identified in academic diabetes clinics and were matched by age, sex, BMI, ethnicity, and diabetes status with 10 women with control T2DM without lipodystrophy. All patients were characterized by clinical evaluation and hyperinsulinemic clamp.

Results: Patients with T2DM and PLL exhibited symmetrical loss of subcutaneous fat in forearms, or forearms plus calves, and acanthosis nigricans. Maximally stimulated glucose disposal rates were markedly reduced by 56% in the T2DM with PLL group compared with the control T2DM patients, whether normalized by body weight or surface area. Most PLL patients exhibited little or no insulin-mediated glucose uptake after subtraction of non-insulin-mediated glucose uptake. The T2DM with PLL group also had greater elevations in hepatic transaminases and triglycerides and earlier onset of diabetes compared with control T2DM.

Conclusions: T2DM with PLL represents a previously unrecognized phenotype of lipodystrophy and of T2DM. These T2DM patients exhibit symmetrical lipodystrophy of the distal limbs, acanthosis nigricans, marked insulin resistance with little insulin-mediated glucose uptake, hypertriglyceridemia, and hepatic transaminase elevations, which are greater in severity than observed in patients with common T2DM.

Figure 1

Patient 1 is shown with arrows indicating lipodystrophy of the forearms, thighs, and legs.

Figure 2

Comparison of GDR and total triglycerides and cholesterol. A: GDRs were assessed using the hyperinsulinemic-euglycemic clamp technique and normalized per kilogram of body weight. Mean ± SE values were significantly lower in 10 patients with T2DM and PLL (T2DM+PLL) compared with 10 patients with common T2DM (2.26 ± 0.42 vs. 4.74 ± 0.77 mg/min/kg; P < 0.05). B: In each subject, the value for non-insulin–mediated glucose disposal (1.6 mg/min/kg; see Insulin resistance: GDRs and fasting insulin levels) was subtracted from the total GDR during the clamp to obtain the insulin-mediated GDR. The mean ± SE value for insulin mediated glucose uptake in T2DM+PLL was minimal and markedly reduced compared with common T2DM (0.64 ± 0.42 vs. 3.12 ± 0.77 mg/min/kg; P < 0.05). C: The mean ± SE value for triglycerides was increased in 10 patients with T2DM and PLL (T2DM+PLL) compared with 10 patients with common T2DM (543 ± 175 vs. 134 ± 28 mg/dL; P < 0.05). D: Mean ± SE levels of total cholesterol were statistically similar in comparing the T2DM groups with and without PLL (223 ± 14 vs. 184 ± 17 mg/dL; P = 0.10). Data in all panels were controlled for BMI, age, and race.

Figure 3

Measurement of liver function. Values for AST (A), ALT (B), and ALP (C) were expressed as percentage of upper limit of the normal reference range and for total bilirubin (D) as IU/L. All panels compare mean ± SE values in patients with T2DM and PLL (T2DM+PLL) and in patients with common T2DM. The mean was statistically increased in T2DM+PLL for AST, ALT, and total bilirubin (all P < 0.05) but not for ALP (P = NS). Data in all panels were controlled for BMI, age, and race.