TOPLINE:

Different subgroups of patients with adult-onset diabetes showed different rates of comorbidities and mortality outcomes. Patients with severe insulin-resistant diabetes (SIRD), a high-risk subtype, were most likely to have kidney, liver, and heart diseases despite having only mild hyperglycemia, and some of these conditions were present even before diabetes was diagnosed.

METHODOLOGY:

• Diabetes is diagnosed and treated primarily on the basis of blood glucose levels, but symptoms and disease progression can differ depending on pathophysiology, environment, genetics, and the risk for other health conditions.
• A prospective cohort study evaluated the prevalence and incidence of comorbidities and mortality outcomes in five subgroups of patients with adult-onset diabetes: severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), SIRD, mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD).
• The analysis included 19,076 adults (11,171 male and 7905 female) diagnosed between January 2008 and April 2022; inclusion criteria were age 18 years or older, absence of pancreatitis, availability of complete cluster variable data, and enrollment within 1 year of diagnosis.
• Glutamic acid decarboxylase (GAD) antibodies, homeostasis model assessment 2 beta-cell function and insulin resistance indices, BMI, A1c levels, and age at diagnosis were used to group individuals into diabetes subgroups.
• The main outcomes were rates of stage IIIa and IIIb chronic kidney disease, micro- and macroalbuminuria, kidney failure, steatotic liver disease, peripheral vascular disease, myocardial infarction, heart failure, atrial fibrillation, stroke, hypertension, diabetic retinopathy, all-cause and cardiovascular mortality, and other outcomes.

TAKEAWAY:

• Compared with the MARD group, the SAID and SIDD groups had the highest A1c levels; these groups also showed increased risks for retinopathy (adjusted hazard ratio [aHR] for SAID, 1.35; aHR for SIDD, 2.11) and neuropathy (aHR for SAID, 2.58; aHR for SIDD, 2.13) during a median follow-up duration of 4.8 years.
• Both SIDD and SIRD groups showed increased risks for incident kidney diseases, including kidney failure (aHR for SIDD, 2.94; aHR for SIRD, 3.41), and myocardial infarction (aHR for SIDD, 1.44; aHR for SIRD, 1.51); the risk for steatotic liver disease was elevated only in the SIRD group (aHR, 3.29), and the risks for atrial fibrillation (aHR for SIRD, 1.32; aHR for MOD, 1.58) and heart failure (aHR for SIRD, 1.55; aHR for MOD, 1.33) were elevated in the SIRD and MOD groups.
• The SIDD, SIRD, and MOD groups exhibited the highest risk for total mortality (aHR, 1.41-1.52).
• Certain cardiovascular, renal, and hepatic comorbidities were already present in patients in the SIRD group at the time of diagnosis of diabetes. This suggests that SIRD is a high-risk diabetes subtype even though it was not identified by conventional glycemia-based risk factors.

IN PRACTICE:

“[The authors] help to highlight insulin resistance as a primary cause of diabetes-related complications, operating largely independently of obesity and glycemic control,” experts wrote in an accompanying editorial.

SOURCE:

The study was led by Olof Asplund, PhD, Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, Malmö, Sweden. It was published online in The Lancet Diabetes & Endocrinology.

LIMITATIONS:

The use of clinically determined diagnoses could result in underdiagnosis, particularly for conditions such as neuropathy and steatotic liver disease. Although GAD antibodies were the most prevalent autoantibody in adult-onset type 1 diabetes, the presence of other autoantibodies could not be excluded. Furthermore, therapeutic interventions and the natural progression of diabetes could change cluster variables, including autoantibody presence, potentially affecting classification at later timepoints.

DISCLOSURES:

The study received support from the Swedish Research Council, Avtal om Lakarutbildning och Forskning Swedish government grants, Diabetes Wellness Sweden, the Novo Nordisk Foundation, AstraZeneca, and other sources. Some authors reported being employees of, receiving research funding from, and/or holding stock in AstraZeneca and/or Novo Nordisk.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.