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Unexplained reciprocal regulation of diabetes and lipoproteins

Higuchi, Seia,b,*; Izquierdo, M., Concepcióna,b,*; Haeusler, Rebecca, A.a,b

Current Opinion in Lipidology: June 2018 - Volume 29 - Issue 3 - p 186–193
doi: 10.1097/MOL.0000000000000521
LIPID METABOLISM: Edited by Marit Westerterp and Bart van de Sluis

Purpose of review Type 2 diabetes is associated with a characteristic dyslipidemia that may exacerbate cardiovascular risk. The causes of, and the effects of new antihyperglycemia medications on, this dyslipidemia, are under investigation. In an unexpected reciprocal manner, lowering LDL-cholesterol with statins slightly increases the risk of diabetes. Here we review the latest findings.

Recent findings The inverse relationship between LDL-cholesterol and diabetes has now been confirmed by multiple lines of evidence. This includes clinical trials, genetic instruments using aggregate single nucleotide polymorphisms, as well as at least eight individual genes – HMGCR, NPC1L1, HNF4A, GCKR, APOE, PCKS9, TM6SF2, and PNPLA3 – support this inverse association. Genetic and pharmacologic evidence suggest that HDL-cholesterol may also be inversely associated with diabetes risk. Regarding the effects of diabetes on lipoproteins, new evidence suggests that insulin resistance but not diabetes per se may explain impaired secretion and clearance of VLDL-triglycerides. Weight loss, bariatric surgery, and incretin-based therapies all lower triglycerides, whereas SGLT2 inhibitors may slightly increase HDL-cholesterol and LDL-cholesterol.

Summary Diabetes and lipoproteins are highly interregulated. Further research is expected to uncover new mechanisms governing the metabolism of glucose, fat, and cholesterol. This topic has important implications for treating type 2 diabetes and cardiovascular disease.

aColumbia University College of Physicians & Surgeons, Naomi Berrie Diabetes Center

bDepartment of Pathology and Cell Biology, New York, NY

Correspondence to Rebecca A. Haeusler, Columbia University Medical Center, 1150 Saint Nicholas Avenue, Room 303A, New York, NY 10032 USA. Tel: +1 212 851 4899; e-mail:

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