Glycemic Control and Complications in Type 2 Diabetes Mellitus
Section snippets
The Current State of Diabetes Care
Approximately 24 million persons in the United States have diabetes, of which type 2 diabetes accounts for the vast majority of cases.1 Based on the National Health and Nutrition Examination Survey (NHANES) 1999 to 2002 data, ∼73 million Americans have diabetes or impaired fasting glucose (IFG), a condition that increases the risk for diabetes.2 A retrospective cohort study using the database of a healthcare maintenance organization, showed that nearly 25% of individuals with newly acquired
Glycemic Control and Microvascular Complications
The incidence and prevalence of neuropathy, retinopathy, and nephropathy increase with the duration of diabetes.16 The United Kingdom Prospective Diabetes Study (UKPDS) 35 demonstrated that HbA1c is strongly related to microvascular effects in patients with type 2 diabetes. Over a mean follow-up of 10 years, which was equivalent to the duration of type 2 diabetes in the study, a 1% reduction in HbA1c was associated with a 37% reduction in microvascular complications and a 43% reduction in
Hyperglycemia and Macrovascular Disease
Hyperglycemia, as measured by HbA1c, is a predictor of coronary heart disease (CHD) risk. In a Finnish study that followed elderly men and women (of whom ∼16% and ∼19% had type 2 diabetes, respectively, at baseline) for up to 3.5 years, HbA1c >7.9% were associated with a 21% incidence of CHD-related events and a 12% incidence of CHD mortality (P <0.05).28 In the Norfolk cohort of the European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk), 82% of the excess mortality
Diabetes Mellitus: Roles of Glucotoxicity and Glucolipotoxicity
Many clinicians believe that glucotoxicity plays a role in β-cell function, amplifies lipotoxicity, and reduces β-cell mass. Under current treatment models, glucotoxicity would not be considered a complication of type 2 diabetes because antidiabetes treatment is warranted only after a patient has reached a certain degree of β-cell dysfunction, as evidenced by fasting hyperglycemia. Just as microvascular and macrovascular complications begin before current treatment protocols prescribe
Summary
Almost 50% of patients with type 2 diabetes have HbA1c above the generally recommended goal of <7%. However, microvascular complications may occur in many patients whose HbA1c is below the current target. A recent understanding of the biochemical pathology of microvascular complications may lead to development of novel disease markers and treatments to help identify and manage patients before they are diagnosed with type 2 diabetes.
Macrovascular complications may represent the greatest cause of
Author Disclosures
The author of this article has disclosed the following industry relationships:
Mark Stolar, MD, is a member of Speakers' Bureaus of Amylin Pharmaceuticals, Inc., Novo Nordisk, and Takeda Pharmaceuticals North America, Inc.; and serves on the advisory board of Takeda Pharmaceuticals North America, Inc.
Acknowledgment
I thank Jonathan Wert, MD, of BlueSpark Healthcare Communications for literature research and editorial assistance.
References (56)
- et al.
Diagnosis and management of prediabetes in the continuum of hyperglycemia: when do the risks of diabetes begin?A consensus statement from the American College of Endocrinology and the American Association of Clinical Endocrinologists
Endocr Pract
(2008) - et al.
Albuminuria is evident in the early stages of diabetes onset: results from the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab)
Am J Kidney Dis
(2004) - et al.
Prevalence, treatment, and control of diagnosed diabetes in the US National Health and Nutrition Examination Survey 1999-2004
Ann Epidemiol
(2008) Diabetic complications: the importance of glucose control
Endocrinol Metab Clin North Am
(1996)Atherosclerosis in diabetes: the role of hyperinsulinemia
Metabolism
(1988)- et al.
Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study
Lancet
(2002) - et al.
Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials
Am Heart J
(2006) Pancreatic beta-cell loss and preservation in type 2 diabetes
Clin Ther
(2003)Pathogenesis of type 2 diabetes mellitus
Med Clin North Am
(2004)General information and national estimates on diabetes in the United States
(2007)
Prevalence of diabetes and impaired fasting glucose in adults in the US population: National Health and Nutrition Examination Survey 1999–2002
Diabetes Care
Progression from newly acquired impaired fasting glucose to type 2 diabetes
Diabetes Care
Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population: the Hoorn Study
JAMA.
Executive summary: standards of medical care in diabetes—2009
Diabetes Care
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus
Endocr Pract
Glycemic control from 1988 to 2000 among US adults diagnosed with type 2 diabetes
Diabetes Care
Relationship between diabetes and mortality: a population study using record linkage
Diabetes Care
Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction
N Engl J Med
Predictors of health care costs in adults with diabetes
Diabetes Care
The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus
N Engl J Med
Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
Lancet
Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1946 and 1973
Diabetes Care
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study
BMJ
The pathobiology of diabetic complications: a unifying mechanism
Diabetes
Overexpression of glucose transporters in rat mesangial cells cultured in a normal glucose milieu mimics the diabetic phenotype
J Clin Invest
Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells
Diabetes
Nerve conduction and aldose reductase inhibition during 5 years of diabetes or galactosaemia in dogs
Diabetologia
Hyperglycemia inhibits calcium entry and hypertrophy in neonatal cardiomyocytes
Diabetes
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Statement of author disclosure: Please see the Author Disclosures section at the end of this article.