Despite having mild hyperglycemia for approximately 50 years, patients with a mutation in the gene encoding the enzyme glucokinase had a low prevalence of clinically significant vascular complications, findings that provide insights into the risks associated with isolated mild hyperglycemia, according to a study in the January 15 issue of JAMA.
"In both type 1 and type 2 diabetes, hyperglycemia [abnormally high blood sugar] is associated with microvascular complications over time. Intensive treatment to lower blood glucose levels reduces the development of microvascular complications," according to background information in the article. Certain patients with glucokinase (GCK) mutations have mild fasting hyperglycemia from birth, resulting in an elevated glycated hemoglobin (HbA1c) level that mimics recommended levels for type 1 and type 2 diabetes.
Anna M. Steele, Ph.D., of the University of Exeter, United Kingdom, and colleagues assessed the prevalence and severity of microvascular and macrovascular complications in patients with GCK mutations to provide additional information about the relationship between current glycemic targets and diabetes-related complications. The study, conducted in the United Kingdom between August 2008 and December 2010, included 99 GCK mutation carriers (median [midpoint] age, 49 years), 91 nondiabetic, nonmutation carrier relatives (control) (median age, 52 years), and 83 individuals with young-onset type 2 diabetes (YT2D), diagnosed at age 45 years or younger (median age, 55 years). Median HbA1c was 6.9 percent in patients with the GCK mutation, 5.8 percent in controls, and 7.8 percent in patients with YT2D.
The prevalence of clinically significant microvascular complications (such as retinopathy, nephropathy, and neuropathy) was low in patients with a GCK mutation (1 percent) and the control group (2 percent). In contrast, 36 percent of the YT2D group had evidence of clinically significant microvascular disease. Thirty percent of patients with GCK had retinopathy compared with 14 percent of controls and 63 percent of patients with YT2D.