1. Glucokinase (GCK) mutation carriers, who are in a state of mild hyperglycemia since birth, demonstrated a low prevalence and severity of micro- and macrovascular complications.
Evidence Rating Level: 3 (Average)
Study Rundown: Although Hba1c targets for non-pregnant diabetics are currently recommended to be less than 7%, the determination of an “ideal” value for Hba1c remains an elusive and controversial topic. While overt hyperglycemia bears known detrimental effects on the vascular system, few studies have examined the risks associated with the chronic, mild hyperglycemia, which corresponds to our current Hba1c target guidelines. As individuals with heterozygous, inactivating glucokinase (GCK) mutations are in a state of mild hyperglycemia since birth that mimics current target guidelines, GCK mutation carriers were utilized in this study to assess such risks. Although the low prevalence and severity of vascular complications seen in GCK mutation carriers in this study largely supports current treatment guidelines, it is important to recognize that there remain inherent differences between GCK mutation carriers and type 1 or type 2 diabetics that may limit the generalizability of these study findings.
Relevant Reading: Effects of intensive glucose lowering in type 2 diabetes
In-Depth [cross-sectional study]: This study assessed the prevalence and severity of nephropathy, retinopathy, peripheral neuropathy, peripheral vascular disease, and cardiovascular disease across three groups: GCK mutations carriers; a control group of non diabetic, familial, non mutation carriers; and individuals with young-onset type 2 diabetes (YT2D) diagnosed prior to the age of 45. The median duration of hyperglycemia in GCK mutation carriers was 48.6 years. While GCK mutation carriers demonstrated a low prevalence of clinically significant microvascular complications that was not significantly different from that of the control group (p=0.52), the YT2D group demonstrated a prevalence of 36% (95%CI, 25%-47%). Similarly, while GCK mutation carriers demonstrated a low prevalence of clinically significant macrovascular complications that was not significantly different from that of the control group (p=.09), the YT2D group demonstrated a prevalence of 30% (95%CI, 21%-41%).
By Priyanka Vedak and Rif Rahman
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