PRIMEVIEW

TYPE 2 DIABETES MELLITUS

For the Primer, visit doi:10.1038/nrdp.2015.19

Type 2 diabetes mellitus (T2DM) is a EPIDEMIOLOGY

MANAGEMENT Weight
chronic metabolic disorder associated
management
with hyperglycaemia caused by impaired should always 2013 2035
insulin secretion and insulin resistance. accompany
T2DM therapy

ZZ
MECHANISMS

Impaired insulin secretion in T2DM is caused

Z
Although T2DM has a
by pancreatic β-cell dysfunctioning owing to 380 million adults 600 million adults
strong genetic component, HOTEL
lipotoxicity, glucotoxicity and resistance to with T2DM with T2DM
the vast majority of T2DM DRIVE-THRU
incretins (intestinal hormones that stimulate insulin cases are potentially
secretion). Peripheral organs — including the liver, controllable by a T2DM is the most common type of diabetes,
muscle and kidney — become insulin resistant, healthy lifestyle (accounting for >90% of cases). T2DM has
leading to reduced glucose uptake from blood, become a global health problem and parallels
excessive glucose reabsorption by the kidney and the obesity epidemic. BMI >25 is the single most
increased gluconeogenesis, all of which contribute important risk factor. However, the prevalence
to hyperglycaemia. Insulin resistance is the result of of T2DM has increased dramatically in China
impaired insulin receptor signalling. Causes of the and India, despite the low prevalence of obesity.
vel
insulin resistance include genetic abnormalities,
um glucose le This observation might be explained by different
ectopic lipid accumulation, mitochondrial Ser fat-versus-muscle-mass ratios, different fat
dysfunction, inflammation and endoplasmic tissue distribution and a greater severity of
reticulum stress. The severity and duration of
hyperglycaemia determine the risk of microvascular
T2DM the β-cell failure.

complications (retinopathy, nephropathy and

neuropathy). Macrovascular complications ETES
IAB SCREENING
(myocardial infarction, peripheral vascular disease D
and stroke) result from dyslipidaemia, hypertension, PRE
hyperglycaemia and inflammation. NORMAL Screening for T2DM is recommended for adults
who are ≥45 years of age, obese and/or have
Successful glycaemic control requires a multifactorial approach. a family history, especially since randomized
Available drugs target hepatic glucose production (metformin), controlled clinical trials have shown that intensive
promote insulin secretion, increase sensitivity to insulin, act on lifestyle interventions, sometimes combined with
the incretin axis or target intestinal and renal glucose absorption. medication,
are effective in
Insulin delaying and T2DM is preceded by
even preventing prediabetes, in which
DIAGNOSIS T2DM. However, patients have higher
pharmacological than normal glycaemic
The clinical presentation, underlying Diagnosis mainly depends on serum are considered as prediabetes interventions to levels. Disease
progression to overt
pathophysiology and disease glucose levels. Cut-off values have and of >126 mg per dl as T2DM. prevent T2DM
T2DM is common, with
progression vary considerably been formulated based on the risk Glycated haemoglobin A1c (HbA1c) have not been
an annual conversion
between individuals, making a clear of complications. Fasting glucose levels of ≥6.5% have been added as approved in
rate of 3–11% per year.
classification of T2DM difficult. levels of more than ~100 mg per dl a diagnostic criteria. most countries.

Designed by Laura Marshall Article number: 15039; doi:10.1038/nrdp.2015.39; published online 23 July 2015
© 2015 Macmillan Publishers Limited. All rights reserved