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Ethnicity and Type 2 Diabetes: Special Emphasis on Pathogenesis and Management

Authors: Melissa E. Clarke, MDFaculty and Disclosures


Kwame Osei, MD, Professor of Medicine & Exercise Physiology, and Director, Division of Endocrinology Diabetes and Metabolism at Ohio State University, Columbus, Ohio, presented this session.

Epidemiology of Diabetes

There are 17 million Americans (5.9% of the population) who have diabetes mellitus (DM), with up to 6.4 million not yet diagnosed and almost 1 million new cases added yearly. Of these cases, 90% to 95% of the cases are type 2 diabetes.[1] As the leading cause of blindness, end-stage renal disease, and non-traumatic amputations in adults, diabetes costs the US healthcare system over $132 million a year, which accounts for one seventh of the healthcare dollars spent.[2]

At every age group, African Americans have one of the highest incidences of diabetes in the United States, with over 20% of African Americans between 60 and 74 years old having the disease. The rate of type 2 diabetes is growing fastest in ethnic minorities, including African Americans, Mexican Americans, and Native Americans. The disease is most prevalent among Native Americans in the southeastern United States, with 27.8% of the population affected. On average, Native Americans, including Alaska Natives, are 2.2 times as likely to have diabetes as non-Hispanic whites of similar age (Figure).[3] The demographics are even more striking among children of minority groups where the rate of type 2 diabetes is increasing rapidly as compared to the rate in their white counterparts.[4] African Americans account for 75% of all childhood cases of type 2 diabetes, whites less than 25%. The reverse is true for childhood cases of type 1 diabetes: whites account for 82%, while African Americans are only 18% of the total cases.[5]

Figure. Age-adjusted total prevalence of diabetes in people aged 20 years or older, by race/ethnicity -- United States, 2002.
Source: 1999-2001 National Health Interview Survey and 1999-2000 National Health and Nutrition Examination Survey estimates projected to year 2002. 2002 outpatient database of the Indian Health Service.

Reasons for Increased Prevalence of Diabetes in Various Ethnicities. According to the 2003 report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, in addition to race/ethnicity, the other risk factors for type 2 DM include:[6]

  • A family history of diabetes;

  • BMI > 25 kg/m2;

  • Habitual physical inactivity;

  • Previously identified impaired fasting glucose (100-125 mg/dL) or impaired glucose tolerance test (2-hour postprandial glucose between 140 and 200 mg/dL);

  • Hypertension (> 140/90 mm Hg in adults);

  • High-density lipoprotein-C < 35 mg/dL and/or triglycerides > 250 mg/dL;

  • History of gestational diabetes or delivery of a baby weighing > 9 lb; and

  • Polycystic ovarian disease.

The main theory regarding why diabetes is more prevalent among some ethnic groups is the "thrifty gene" theory proposed in 1962 by geneticist James Neel to help explain why many Pima Indians are overweight.[7] Populations, who for thousands of years relied on farming, hunting, and fishing for food, experienced alternating periods of feast and famine. To adapt to these extreme changes in caloric needs, these people developed a "thrifty gene" that allowed them to store fat during times of plenty so that they would not starve during times of famine. However, once these populations adopted the typical Western lifestyle, with less physical activity, a high fat diet, and access to a constant supply of calories, this gene began to work against them, continuing to store calories in preparation for famine. Once protective, it is now contributing to their retention of unhealthy amounts of fat.

Obesity, Beta-Cell Dysfunction, and Insulin Resistance

The exact genetic abnormality that threatens insulin production is still unknown. The natural history of the disease often starts with obesity and leads to impaired fasting glucose, diabetes, and uncontrolled hyperglycemia. However, obesity is not the final determinant of developing type 2 diabetes because the disease does not develop in all people who are obese. Dysfunction and failure of islet beta cells in the pancreas must occur for the diagnosis of diabetes to occur as well as peripheral insulin resistance. There is a loss of the early phase of insulin secretion by beta cells in response to a glucose load, resulting in a severely blunted insulin response.[8] The UK Prospective Diabetes Study (UKPDS) showed that beta-cell function declines progressively.[9] In fact, the decline typically starts 10 years before symptoms are even seen and the diagnosis of type 2 diabetes is made. By the time impaired glucose tolerance is seen, 50% of beta-cell function is gone (pre-diabetes). Concurrent with beta-cell dysfunction, peripheral insulin resistance causes enhanced liver production of glucose, leading to further hyperglycemia. Adipose tissue, as one of the largest endocrine organs in the body, produces a variety of substances, including tumor necrosis factor-alpha (TNF-alpha), which increases lipolysis and affects metabolism of glucose and fats. This process, in turn, causes an increase in plasma free fatty acids (FFA), leading to the development of type 2 diabetes and hypertension. Studies show that the amount of TNF-alpha released by adipocytes positively correlates with the body mass index.[10]

There are differences at the biochemical level that account for the varying rates of diabetes among ethnic groups. These include differences in hepatic glucose production, gluconeogenesis, peripheral insulin sensitivity, and pharmacogenetics. African Americans maintain normoglycemia through a greater insulin response to an oral glucose load than whites. This genetic difference is seen in people of African descent throughout the world, no matter where tested.[11] This reduced insulin sensitivity is seen in all ethnic groups compared to whites.[12] African Americans were also found to have lower adiponectin levels than whites. Adiponectin, which is synthesized and secreted by adipose tissue, improves insulin sensitivity, FFA metabolism, protects against the development of DM and is anti-atherogenic. African-American patients with impaired glucose tolerance have higher levels of adiponectin than those with diabetes.[13] Therefore, a possible mechanism for treatment and protection from type 2 DM is to stimulate adiponectin production through diet and weight loss.

The Case for Tight Glycemic Control

Goals for glycemic control differ between the American Diabetes Association (ADA) 2003 Clinical Practice Recommendations and the 2002 American College of Endocrinology (ACE) Consensus Statement on Guidelines for Glycemic Control (Table).

Table. Recommended Goals for Glycemic Control from American Diabetes Association and American College of Endocrinology

Index Normal ADA Goal ACE Target
Fasting plasma glucose (mg/dL) < 110 90-130 < 110
Postprandial plasma glucose (mg/dL) < 140 < 180 < 140
A1C(%) < 6 < 7 < 6.5
A1C = glycosolated hemoglobin

The UKPDS showed that in diabetics, glucose control, as measured by mean fasting plasma glucose and A1C concentration, eroded over a 9-year period.[14] Those treated with conventional oral agents, as compared to insulin, experienced a much faster erosion of control of both plasma glucose and A1C levels. The UKPDS group also established the need for tight glycemic control, showing that for every 1% drop in A1C, there was a decrease in all diabetes-related endpoints including the risk of myocardial infarction, stroke, and microvascular disease.[15] When one measures A1C, one is measuring the degree to which fasting hyperglycemia and mealtime glucose excursions were controlled in a given time.[16] Fasting glucose is influenced by hepatic glucose production and hepatic sensitivity to insulin. Postprandial glucose is governed by pre-prandial glucose, insulin secretion, glucose load from a meal, and insulin sensitivity in peripheral tissues.

Pharmacologic Therapy: Mono or Combination. Several different oral agents are effective in achieving tight glycemic control, and each functions by a different mechanism. Insulin secretagogues as a whole act at the following sites: (1) the intestine to decrease glucose absorption, (2) muscle and adipose tissue to increase glucose uptake and decrease insulin resistance, (3) the pancreas to stimulate insulin secretion, and (4) the liver to decrease hepatic glucose output. Metformin inhibits hepatic gluconeogenesis, may increase peripheral insulin sensitivity, and can be used in conjunction with a number of other agents including metiglinides, netlitanides, and thiazolidinediones (TDZs). TDZs, one of the more recent agents, decrease hepatic glucose output, and improve glucose uptake and insulin sensitivity peripherally. Rosiglitazone (Avandia), one of the TDZs, was very effective in increasing adiponectin levels in all groups.[17]

Despite the effectiveness of certain monotherapies, over time they may diminish in effectiveness. The UKPDS sought to answer whether monotherapy with dietalone, insulin, sulfonylurea, or metformin most frequently attained thetarget fasting plasma glucose (FPG) concentration of less than7.8 mmol/L (140 mg/dL) or glycosylatedA1Cbelow 7%.[18] After 3 months on a low-fat, high-carbohydrate,high-fiber diet, patients were randomized to 1 of the monotherapy agents. Each therapeutic agent, as monotherapy, increased2- to 3-fold the proportion of patients who attainedA1C below 7% compared with diet alone. However, the proportion of patients who maintained targetglycemic levels declined markedly over 9 years of follow-up. The progressivedeterioration of diabetes control was such that after 3 years,approximately 50% of patients needed multiple therapies to attain glycemictarget levels. There are many options for combination therapy for type 2 DM. They include:

  • Sulfonylurea + metformin;

  • Sulfonylurea + pioglitazaone or rosiglitazone;

  • Metformin+ pioglitazaone or rosiglitazone;

  • Metformin + repaglinide;

  • Metformin + glyburide;

  • GLP -1 analogue + TDZs or metformin; or

  • Acarbose or miglitol + any other glucose-lowering drug.

Future Questions

Several questions still remain to be answered in the pathogenesis of DM including (1) are there racial/ ethnic differences in the non-conventional mediators, such as adipocytokines, that contribute to the development of type 2 DM and its long-term complications? (2) Are there racial differences in glycemic thresholds, fasting plasma glucose, or A1C, for the development of long-term complications among different racial/ethnic populations? (3) Are there constitutive and genetic differences in the development of type 2 DM and its complications?


  1. NIDDK. Diabetes Statistics. NIH Publication no. 96-3926; November 1997 (updated February 1998).
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