Differences in complication patterns in subgroups of type 2 diabetes according to insulin resistance and beta-cell function

Abstract

This study aimed to determine whether the patterns of diabetic complications differed when patients with type 2 diabetes mellitus (T2DM) were simply classified according to insulin sensitivity and beta-cell function. This observational study included 8861 patients with T2DM who underwent concurrent testing for fasting glucose, fasting insulin, and one or more diabetic complications. We categorized the patients into four groups according to insulin sensitivity and beta-cell function. Compared with the reference group (mild insulin resistance and beta-cell dysfunction), the "severe beta-cell dysfunction" group had lower odds of chronic kidney disease [adjusted odds ratios (aOR) 0.611]. The "severe insulin resistance" group had higher odds of carotid artery plaque presence (aOR 1.238). The "severe insulin resistance and beta-cell dysfunction" group had significantly higher odds of large fiber neuropathy (aOR 1.397, all p < 0.05). After a median of five years of follow-up, this group distinction did not lead to a difference in risk of new diabetic retinopathy or chronic kidney disease. In addition, there was no significant difference among the groups in plaque progression risk over 8-10 years in the longitudinal follow-up analysis. The patterns of complications differ when patients with T2DM are classified according to insulin resistance and beta-cell dysfunction. However, there were no differences in the risk of developing new complications.

Figure 1

Odds of accompanying diabetic complications or hepatic steatosis by group according to insulin sensitivity and beta-cell function. Odds ratios of (a) chronic kidney disease (eGFR < 60 mL/min/1.73 m²), (b) hepatic steatosis, (c) plaque presence, (d) large fiber neuropathy, and (e) diabetic retinopathy. The results were adjusted for age, sex, diabetes duration, systolic blood pressure, diastolic blood pressure, time of enrollment, method of insulin measurement, BMI, HbA1c levels, LDL cholesterol levels, eGFR (not included in the analysis depicted in a), statin use, smoking status, alcohol consumption, and physical activity. Group 1. Reference (mild insulin resistance and beta-cell dysfunction) group. Group 2. “Severe beta-cell dysfunction” group. Group 3. “Severe insulin resistance” group. Group 4. “Severe insulin resistance and beta-cell dysfunction” group. BMI body mass index, LDL low-density lipoprotein, eGFR estimated glomerular filtration rate. *p < 0.05 versus group 1.

Figure 2

Risk of developing diabetic complications by group. Kaplan–Meier curve and hazard ratios of (a) retinopathy and (b) chronic kidney disease. The results were adjusted for age, sex, diabetes duration, systolic blood pressure, diastolic blood pressure, time of enrollment, BMI, HbA1c levels, LDL cholesterol levels, eGFR (not included in the analysis depicted by [b]), statin use, smoking status, alcohol consumption, and physical activity. Group 1. Reference (mild insulin resistance and beta-cell dysfunction) group. Group 2. “Severe beta-cell dysfunction” group. Group 3. “Severe insulin resistance” group. Group 4. “Severe insulin resistance and beta-cell dysfunction” group. aHR adjusted hazard ratio, CKD chronic kidney disease.

Figure 3

Risk of carotid plaque progression by group. Odds ratio of carotid plaque progression. The results were adjusted for age, sex, diabetes duration, systolic blood pressure, diastolic blood pressure, time of enrollment, BMI, HbA1c levels, LDL cholesterol levels, eGFR, statin use, smoking status, alcohol consumption, and physical activity. Group 1. Reference (mild insulin resistance and beta-cell dysfunction) group. Group 2. “Severe beta-cell dysfunction” group. Group 3. “Severe insulin resistance” group. Group 4. “Severe insulin resistance and beta-cell dysfunction” group. aOR adjusted odds ratio.

Figure 4

Summary of the group characteristics and risk of accompanying diabetic complications. DM diabetes mellitus, BMI body mass index, WC waist circumference, HOMA homeostatic model assessment, IR insulin resistance, HDL high-density lipoprotein.