Intramyocellular Triglyceride Content During the Early Course of Type 1 and Type 2 Diabetes

Abstract

Intramyocellular lipid content (IMCL) is elevated in insulin-resistant humans, but it changes over time, and relationships with comorbidities remain unclear. We examined IMCL during the initial course of diabetes and its associations with complications. Participants of the German Diabetes Study (GDS) with recent-onset type 1 (n = 132) or type 2 diabetes (n = 139) and glucose-tolerant control subjects (n = 128) underwent 1H-MRS to measure IMCL and muscle volume, whole-body insulin sensitivity (hyperinsulinemic-euglycemic clamps; M-value), and cycling spiroergometry (VO2max). Subgroups underwent the same measurements after 5 years. At baseline, IMCL was ∼30% higher in type 2 diabetes than in other groups independently of age, sex, BMI, and muscle volume. In type 2 diabetes, the M-value was ∼36% and ∼62% lower compared with type 1 diabetes and control subjects, respectively. After 5 years, the M-value decreased by ∼29% in type 1 and ∼13% in type 2 diabetes, whereas IMCL remained unchanged. The correlation between IMCL and M-value in type 2 diabetes at baseline was modulated by VO2max. IMCL also associated with microalbuminuria, the Framingham risk score for cardiovascular disease, and cardiac autonomic neuropathy. Changes in IMCL within 5 years after diagnosis do not mirror the progression of insulin resistance in type 2 diabetes but associate with early diabetes-related complications.

Article highlights: Intramyocellular lipid content (IMCL) can be elevated in insulin-resistant humans, but its dynamics and association with comorbidities remain unclear. Independently of age, sex, body mass, and skeletal muscle volume, IMCL is higher in recent-onset type 2, but not type 1 diabetes, and remains unchanged within 5 years, despite worsening insulin resistance. A degree of physical fitness modulates the association between IMCL and insulin sensitivity in type 2 diabetes. Whereas higher IMCL associates with lower insulin sensitivity in people with lower physical fitness, there is no association between IMCL and insulin sensitivity in those with higher degree of physical fitness. IMCL associates with progression of microalbuminuria, cardiovascular disease risk, and cardiac autonomic neuropathy.

Figure 1

Whole-body insulin sensitivity from M-value (A–C) and IMCL triglyceride content (D–F) from ¹H MRS at baseline and at the 5-year follow-up. A, B, D, and E represent the whole cohort at baseline (glucose-tolerant control [CON] subjects, n = 128; type 1 diabetes [T1D], n = 132; type 2 diabetes [T2D], n = 139), and C and F represent the follow-up cohort (glucose-tolerant control subjects, n = 20; type 1 diabetes, n = 27; type 2 diabetes, n = 38). Sex-specific differences within groups at baseline are shown in B and E (males [M] in darker color, females [F] in bright color). In C and F, hatched columns represent 5-year follow-up (FU) data. Data are presented as mean and SD. P values based on ANOVA by paired or unpaired t tests. BL, baseline; *P < 0.05. #P < 0.05 vs. men within the same group. §P < 0.05 vs. same sex of the T1D group. +P < 0.05 vs. same sex of the control subjects group.

Figure 2

Tridimensional regression describing the impact of physical fitness (VO₂max) on the relationship between IMCL content and whole-body insulin sensitivity (M-value) in recent-onset type 2 diabetes at baseline (n = 139).