Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD)

Carolina Ortiz-Lopez, Romina Lomonaco, Beverly Orsak, Joan Finch, Zhi Chang, Valeria G Kochunov, Jean Hardies, Kenneth Cusi, Carolina Ortiz-Lopez, Romina Lomonaco, Beverly Orsak, Joan Finch, Zhi Chang, Valeria G Kochunov, Jean Hardies, Kenneth Cusi

Abstract

Objective: Prediabetes and type 2 diabetes mellitus (T2DM) are believed to be common and associated with a worse metabolic profile in patients with nonalcoholic fatty liver disease (NAFLD). However, no previous study has systematically screened this population.

Research design and methods: We studied the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients with NAFLD. The control group comprised 20 subjects without NAFLD matched for age, sex, and adiposity. We measured 1) plasma glucose, insulin, and free fatty acid (FFA) concentration during an oral glucose tolerance test; 2) liver fat by magnetic resonance spectroscopy (MRS); 3) liver and muscle insulin sensitivity (euglycemic insulin clamp with 3-[(3)H]glucose); and 4) indexes of insulin resistance (IR) at the level of the liver (HIR(i)= endogenous glucose production × fasting plasma insulin [FPI]) and adipose tissue (Adipo-IR(i)= fasting FFA × FPI).

Results: Prediabetes and T2DM was present in 85% versus 30% in controls (P < 0.0001), all unaware of having abnormal glucose metabolism. NAFLD patients were IR at the level of the adipose tissue, liver, and muscle (all P < 0.01-0.001). Muscle and liver insulin sensitivity were impaired in patients with NAFLD to a similar degree, whether they had prediabetes or T2DM. Only adipose tissue IR worsened in T2DM and correlated with the severity of muscle (r = 0.34; P < 0.001) and hepatic (r = 0.57; P < 0.0001) IR and steatosis by MRS (r = 0.35; P < 0.0001).

Conclusions: Patients with NAFLD may benefit from early screening for T2DM, because the prevalence of abnormal glucose metabolism is much higher than previously appreciated. Regardless of glucose tolerance status, severe IR is common. In patients with T2DM, adipose tissue IR appears to play a major role in the severity of NAFLD.

Figures

Figure 1
Figure 1
Prevalence of NGT, prediabetes (PreDM), and T2DM in patients with and without NAFLD. **P < 0.001 vs. without NAFLD.
Figure 2
Figure 2
Role of hyperglycemia on hepatic insulin sensitivity. A: HIRi (HIRi = fasting EGP [hepatic] × FPI concentration). B: Percentage suppression of hepatic EGP by low-dose insulin infusion. Results are mean ± SEM.*P < 0.1 vs. without NAFLD. †P < 0.05 vs. without NAFLD.
Figure 3
Figure 3
Role of hyperglycemia on adipose tissue insulin sensitivity. A: Adipo-IRi (Adipo-IRi = fasting plasma FFA × FPI concentration). B: Percentage suppression of plasma FFA concentration by low-dose insulin infusion. Results are mean ± SEM. ¶P < 0.04 and P < 0.001 vs. without NAFLD. §P < 0.001 vs. NGT. †P < 0.05 and **P < 0.001 vs. without NAFLD. #P < 0.001 vs. without NGT.

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