About 70% of patients with type 2 diabetes mellitus (T2DM) have NAFLD which is a risk factor for cirrhosis and hepatocellular carcinoma. Many factors may be associated with more severe disease (i.e., insulin resistance, obesity). However, the metabolic profile of T2DM patients spared from having NAFLD and liver fibrosis is unclear. To this end, we recruited 266 patients with a history of T2DM without a known history of NAFLD (age: 59 ± 10 years; female 58.3 %; BMI: 33.0 ± 6.3 kg/m2, A1c: 7.0 ± 1.4 %) attending the outpatient university clinics. We performed a medical history, physical exam and measured routine/metabolic laboratories, liver fat (by CAP score ≥ 274 dB/m) and fibrosis (by liver stiffness measurement or LSM ≥7.0 kPa or F≥1) by elastography. A total of 32% patients did not have NAFLD, but when compared to NAFLD patients there were no differences in terms of age, gender, or race. Those without NAFLD had a lower mean BMI ± SD (29.6 ± 5.2 vs. 34.6 ± 6.2 kg/m2) and better glycemic control (mean A1c: 6.7 ± 1.3% vs. 7.2 ± 1.4%, both p<0.05). Patients without NAFLD had lower plasma ALT levels (mean 21 ± 12 vs. 28 ± 19 U/L; p<0.05). Patients with NAFLD had more severe (hepatic) insulin resistance (IR) (HOMA-IR: 3.0 ± 2.3 vs. 4.9 ± 3.2, p<0.05), with more people having a HOMA-IR ≥3.0 (35% vs. 72%, p<0.05). In multiple regression analysis, with a 95% CI, obesity (OR 4.0, 2.3-7.1), HOMA-IR (OR 3.1, 1.0-5.7), and worse glycemic control (A1c) (OR 1.7, 1.1-2.9) accounted for most of the difference between subjects with vs. without NAFLD. In NAFLD patients, comparing those with vs. without fibrosis, obesity (OR 2.8, 1.6-4.9) and elevated aminotransferases (OR 2.1, 1.3-3.2) accounted for most of the difference among patient. Conclusion: Patients with type 2 diabetes mellitus without NAFLD are usually more insulin sensitive and have a more favorable cardiometabolic profile than those with NAFLD. This highlights the role of insulin resistance and lipotoxicity in the development of NAFLD in this population.


E.Valdez saenz: None. D.Barb: None. M.J.Gurka: None. A.Sharma: None. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. E.Godinez leiva: None. R.Lomonaco: None. S.A.Marangi: None. S.Kalavalapalli: None. M.A.Gonzalez: None. X.Chi: None. A.Ortiz rocha: None. Y.Mohseni: None.


National Institutes of Health (R01120331-01A1)

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