Overview and Risk Factors
Diabetes mellitus (DM) includes a group of metabolic diseases characterized by hyperglycemia, which is attributable to insulin deficiency and/or insulin resistance. It leads to a wide range of complications and, when poorly controlled, can contribute to significant morbidity and mortality (see Diabetes Complications chapter). Three main types of diabetes are recognized:
Type 1 diabetes, accounting for approximately 5% to 10% of total cases, occurs after destruction of the insulin-producing beta-islet cells of the pancreas (usually through an autoimmune process). Most cases present in childhood with polyuria and polydipsia, unexplained weight loss, fatigue, and blurred vision. The condition can also be diagnosed in adults. Type 1 diabetes requires insulin treatment.
Type 2 diabetes, which accounts for more than 80% of diabetes cases, usually presents in adults after a long, asymptomatic course. About 85% of patients are centrally obese, and insulin resistance is typically present. Diabetes manifests when insulin production fails to keep pace with the body's increased need. Prevalence in children is climbing rapidly, due to increasing obesity. Type 2 diabetes is often accompanied by hypertension and lipid abnormalities and is part of the metabolic syndrome. Although symptoms upon initial presentation tend to be much milder in type 2 than in type 1 diabetes, complications are frequent and increase in prevalence over time if metabolic control is poor.
Gestational diabetes mellitus (GDM) accounts for about 2% of diabetes cases. As its name suggests, GDM first appears during pregnancy. Hormones secreted by the placenta--estrogen, progesterone, growth hormone, corticotrophin-releasing hormone, and prolactin--oppose insulin's function, and the pancreas struggles to produce enough insulin to compensate for the greater caloric intake during pregnancy. Treatment with dietary modification and/or drugs (usually insulin) is essential to prevent fetal complications. Although blood glucose levels usually normalize postpartum, many women with GDM eventually develop type 2 diabetes.
Risk factors for type 1 diabetes include:
- Family history. When a first-degree relative has diabetes, the risk of developing type 1 diabetes is about 10% to15%. Many possible genes are under investigation.
- Exposure to bovine milk proteins. Consumption of cow's milk in early childhood has been under investigation as a contributing factor, although it has not yet been definitively established.
- Fetal or childhood Coxsackie virus and enteroviral infections
- Birth weight greater than 4,500 grams.
- Maternal age greater than 25 years.1
- ABO incompatibility-induced jaundice.1
Risk factors for type 2 diabetes include:
- Family history of type 2 diabetes in first- or second-degree relatives.
- Older age.1
- Abdominal obesity.2
- History of gestational diabetes.
- The presence of hypertension and dyslipidemia.
- Ethnic background: African Americans, Latinos, American Indian/Alaska Natives, and Asians and Pacific Islanders have a greater prevalence.
Risk factors for GDM are listed below. In addition, individuals of Asian, African, Native American, and Hispanic ancestry have greater prevalence of GDM than non-Hispanic whites.3 The risk factors for GDM overlap with type 2 diabetes.
- Family history of type 2 diabetes in a first-degree relative.
- A previous abnormal oral glucose tolerance test.
- Glucocorticoid use during pregnancy.
- Polycystic ovarian syndrome.
- Age greater than 25 years.
- A prepregnancy weight at least 10% above ideal body weight.
- Early postpubescent weight gain.
- Previous child with birth weight greater than 9 pounds.
- Previous idiopathic perinatal death or birth defect
- Maternal birth weight greater than 9 pounds or less than 6 pounds.4
Endocrinopathies, such as Cushing's disease, acromegaly, pheochromocytoma, and hyperthyroidism, may impair glucose tolerance and should be ruled out.
Type 1 and Type 2 Diabetes
Diabetes can be diagnosed by any of the following:
- A fasting plasma glucose concentration greater than 125 mg/dL.
- A 2-hour oral glucose tolerance test (GTT) result of 200 mg/dL or greater.
- A random plasma glucose of 200 mg/dL or greater when diabetes symptoms are present.
Normal fasting plasma glucose is less than 100 mg/dL, and the 2-hour GTT is less than 140 mg/dL. Intermediate results reflect impaired fasting glucose (impaired glucose tolerance in the case of GTT), which often precedes an eventual diabetes diagnosis. Hemoglobin A1c (A1c) is not currently accepted for diagnosis of diabetes because it is too insensitive, but it is crucial for clinical management.
Type 1 DM often presents with ketoacidosis, which is caused by partial or total insulin deficiency and normally requires hospital admission and intensive care. Type 1 DM can be confirmed by the identification of islet-cell antibodies or other autoantibodies (eg, anti-glutamic acid dehydrogenase (GAD) or anti-insulin antibodies (ICA). However, some patients have no identifiable cause of islet cell destruction.
Patients initially thought to have type 2 DM but with autoantibodies most likely have lateâ€“onset type 1 diabetes or late-onset autoimmune diabetes. They are unlikely to respond adequately to oral hypoglycemics and will likely require insulin.
Measure of glycemia is the only specific diagnostic test to confirm type 2 diabetes.
Screening for GDM is a routine part of prenatal examinations. Several strategies may be used for diagnosis.
Screening typically occurs between 24 and 28 weeks of gestation and involves a 1-hour challenge with a 50-g carbohydrate load. A venous serum or plasma glucose greater than 129 or 139 (either threshold may be used),5 with sensitivity of 90% and 80%, respectively, is abnormal and necessitates a 3-hour GTT (with 100-g carbohydrate load).
The Fourth International Workshop-Conference on Gestational Diabetes Mellitus established more stringent diagnostic criteria, which are based on the 3-hour GTT and require that 2 of the following 4 criteria to be met:
- Fasting serum glucose concentration >95 mg/dL (5.3 mmol/L).
- One-hour serum glucose concentration >180 mg/dL (10 mmol/L).
- Two-hour serum glucose concentration >155 mg/dL (8.6 mmol/L).
- Three-hour serum glucose concentration >140 mg/dL (7.8 mmol/L).
In pregnancy, mildly abnormal glucose levels can lead to fetal complications, which is why fasting serum glucose greater than 95 mg/dL is considered abnormal and treatment is started very early. Treatment should be considered in women with fasting glucose greater than 90 mg/dL due to the increased risk of macrosomia, which can occur even with a normal GTT.6
Dietary and lifestyle interventions are important for patients with all types of DM (see below). Education for diabetes self-management, which includes self-monitoring of blood glucose, is an important component of treatment.7
Type 1 Diabetes
Insulin is available in several forms, which differ in duration of action.
- Long-acting insulin, such as insulin glargine (Lantus) or insuline detemir (Levemir), can be administered once a day, though some may require injections with these insulins twice daily.
- Regular insulin or fast-acting insulin analogs are short-acting and can be administered before meals to curb postprandial blood glucose elevations.
- NPH has an intermediate length of action and is often administered in the morning and evening. NPH and regular or fast-acting insulin come in premixed ratios such as 70%:30% and 50%:50% for convenience when both insulin types are required. These premixed insulins are primarily used in patients with type 2 diabetes.
- Fast-acting inhalable insulin was approved for use in adults in 2006. Its long-term safety remains unclear, particularly with regard to respiratory health.
Amylin is a beta-cell hormone that is co-secreted with insulin. Pramlinitide, a synthetic amylin analog, is injected at mealtimes along with fast-acting insulin. It reduces postprandial rises in blood glucose concentrations and suppresses appetite, which may lead to weight loss.
Type 2 Diabetes
Biguanides. Metformin is commonly used as a first-line agent. It decreases hepatic gluconeogenesis and increases insulin sensitivity. It is contraindicated in heart failure, renal insufficiency, liver disease, serious infection and illness, and other disease processes.
Sulfonylureas. Glipizide, glyburide, and glimepride are the most commonly used oral antihyperglycemic medications. Glyburide is taken twice a day and may be less desirable for geriatric patients. Glipizide (Glucotrol or Gluctrol XL) and glimiperide (Amaryl) are longer acting, and these should be used cautiously in the elderly and those with any renal insufficiency. Sulfonylureas may cause hypoglycemia.
Thiazolidinediones. Pioglitazone and rosiglitazone increase insulin sensitivity, decrease glucose production, and may also increase insulin secretion. These insulin sensitizers have been
Meglitinides. Nateglinide and repaglinide stimulate insulin secretion, but are shorter acting than sulfonylureas and must be taken with meals.
Alpha-glucosidase inhibitors. Acarbose and miglitol inhibit the conversion of carbohydrates to monosaccharides, and lower postprandial glucose values. Flatulence is a common side effect and may limit compliance, but it generally improves over time.
Incretin Mimetic. Exenatide is an injectable synthetic used to increase insulin secretion at mealtime. It is less likely to cause episodes of low blood sugar or weight gain, compared with insulin or insulin secretogogues.
A patient with presumed type 2 diabetes and autoantibodies is less likely to respond to the above agents. Such patients may require insulin therapy and are at increased risk of ketoacidosis.
Dietary intervention is the first-line treatment for GDM. Adequate control is achieved if fasting plasma glucose is less than 90 mg/dL and 1-hour postprandial glucose is less than 120 mg/dL. When these goals are not met, insulin should be considered. Dietary interventions are discussed in detail under Nutritional Considerations.
Insulin is the best-studied pharmaceutical agent for GDM and the only recommended treatment in the United States. However, metformin and glyburide are used by some obstetricians with some evidence of safety.
For all types of diabetes, good blood-glucose control decreases the risk of complications. Patient medications should be frequently reviewed, because certain pharmaceuticals, such as beta-blockers, thiazides, oral contraceptives, and glucocorticoids, can impair glucose tolerance.
A1c testing should be used as an index of diabetes control. It provides a fairly accurate measurement of the average blood glucose during the previous 2 to 3 months. The A1c goal set by the American Diabetes Association is 7%. However, this value is not a threshold. Risk of complications appears to fall with lower A1c values, and many clinicians aim for an A1c of less than 6.5% through dietary and lifestyle modifications and medications as needed.
Role of Exercise
A sedentary lifestyle is associated with increased risk for impaired glucose tolerance and diabetes.9 Exercise10 and diet-exercise programs that produce weight loss significantly reduce the risk for type 2 diabetes.11,12
Exercise alone has little or no effect on body weight.13 However, in persons with established diabetes, exercise reduces blood glucose and plasma lipid concentrations14 and improves insulin sensitivity. Exercise also reduces cardiovascular complications of diabetes, including high blood pressure, left ventricular diastolic function, arterial stiffness, systemic inflammation, and left ventricular mass.15
Women who either have or are at risk for gestational diabetes can also benefit from exercise. Walking or upper-body exercises (but never in a supine position) may reduce the risk of gestational diabetes16 and help lower glucose levels to the normal range. In women with GDM, exercise has been found to be a useful strategy for helping to maintain blood glucose within the normal range and to control blood glucose without the use of insulin.17 Note: Exercising must be stopped if contractions occur.
Prevention: Type 1 Diabetes
Dietary factors that may influence the risk of type 1 diabetes have been under investigation. The following considerations have emerged as potentially important candidates for preventive strategies, although none has been definitively established as such:
Breast-feeding. In some epidemiologic studies, breast-feeding is associated with reduced risk for developing insulin-dependent diabetes. Longer duration of breast-feeding may reduce risk for type 1 diabetes, presumably by increasing protection against infections, enhancing the infant's immune responses, increasing beta-cell proliferation, and delaying exposure to foreign food antigens.18 An autoimmune mechanism may also be involved (see below). Although breast-feeding is the best choice for infant feeding, ethical and practical difficulties have prevented controlled trials of its effect on diabetes risk.
Avoidance of early introduction of cow's milk. Cow's milk has been temporally related to the diagnosis of diabetes,19 and children with type 1 diabetes have higher levels of antibodies to cow's milk protein that represent independent risk markers for this condition.20 Although it has not yet been proven conclusively that cow's milk is a trigger for type 1 diabetes, the American Academy of Pediatrics concluded that avoiding early exposure to cow's milk may reduce the risk.21
The question of whether the early ingestion of intact foreign proteins contained in cow's milk may increase type 1 diabetes risk may be answered in part by the Trial to Reduce Type 1 Diabetes in the Genetically at Risk (TRIGR) study. This international effort will test the hypothesis that weaning infants to an extensively hydrolyzed formula instead of cow's milk may delay or prevent the onset of type 1 diabetes in genetically susceptible children.22 Although the results of this study are pending, a smaller study with a similar design found that this intervention resulted in a significant protection from positivity for islet cell antibodies.23
Avoiding early introduction of gluten-containing foods. In epidemiologic studies, supplementing infant diets with gluten-containing foods before 3 months of age is associated with increased risk for developing islet cell autoantibodies.24 In some children, both early (before 3 months) and late (after 7 months) introduction of cereals was associated with increased risk of islet autoimmunity, suggesting that there may be a window of exposure to cereals, outside which initial exposure increases islet autoimmunity risk in genetically susceptible children.25
In first-degree relatives of patients with type 1 diabetes and evidence of autoimmunity-related type 1 diabetes, insulin response to intravenous glucose tolerance testing and insulin sensitivity improved on a gluten-free diet, despite the absence of changes in antibody titers.26 A higher prevalence of celiac disease has been observed in children with type I diabetes, compared with other children.27
Researchers are seeking ways to prevent autoimmune attacks of pancreatic beta-cells, with the goal of reducing the risk for developing insulin-dependent diabetes. So far, evidence suggests that the following dietary factors may influence the risk of type 1 diabetes: breast-feeding; vitamin D supplementation;1 and cod liver oil supplementation (a source of vitamin D) during both pregnancy and the infant's first year of life.28 All of these actions are capable of modulating the production of proinflammatory cytokines that are known to be involved in the pathogenesis of type 1 diabetes.29
Prevention: Type 2 Diabetes
Although type 2 diabetes has a strong genetic component, diet and lifestyle significantly affect the likelihood that the disease will manifest and influence its course after diagnosis. The risk for type 2 and gestational diabetes can be decreased by avoiding overweight and by following specific dietary practices.
Individuals in Asia and Africa who follow traditional diets low in animal fat and high in complex carbohydrates and who remain physically active have a far lower incidence of diabetes than those who follow a Western diet and activity pattern.30 Vegetarians also have a lower incidence of diabetes than their omnivorous counterparts.31
These results are probably due to several factors. Intake of saturated fat is associated with impaired glucose tolerance, insulin resistance, gestational diabetes, and type 2 diabetes.32 In contrast, a higher intake of dietary fiber, particularly in the form of fruits and vegetables, results in lower postprandial glucose.33-35 In addition, high-fiber diets often contain micronutrients important in glucose tolerance, including magnesium36 and vitamin E.37
The Diabetes Prevention Program (DPP) demonstrated that dietary changes designed to reduce body weight, combined with regular exercise, can significantly reduce the risk for type 2 diabetes. Specifically, risk reduction was 58% in the group that combined diet and exercise, compared with a 31% reduction for those on drug (metformin) treatment. In individuals age 60 and older the risk reduction was 71% with diet and exercise.11
Based in part on the DPP results, the American Diabetes Association and related organizations currently recommend that patients at risk for type 2 diabetes reduce calorie intake by 500 to 1,000 calories per day and increase activity by walking 30 to 45 minutes per day, 3 to 5 days per week.38
The goals of nutrition therapy in diabetes management include control of glucose to near-normal levels, normalization of serum lipids and blood pressure, and attainment of a healthy weight. Adherence to a healthful diet, regular exercise, and use of medications when necessary may achieve these goals and help minimize the risk of complications.
Current guidelines of the American Diabetes Association prescribe a calorie-controlled meal plan which uses food exchange lists that keep carbohydrate intake reasonably steady throughout the day and from one day to the next. These guidelines also limit saturated fat and cholesterol. Advantages of this approach include flexibility and the allowance of most foods, albeit in limited amounts. However, the use of exchange lists in clinical practice appears to be hampered by limited outcome data,39 the complexity of this approach, and nonadherence, which occurs with almost 25% of food choices.40 Such diets require ongoing education and monitoring, which should generally be provided by a registered dietitian in a series of visits.
Recent studies suggest that low-fat, plant-based diets may be more effective for both glycemic control and reduction of cardiovascular risk factors, particularly plasma cholesterol.41,42 A randomized, controlled trial including 99 individuals with type 2 diabetes showed that, among those whose diabetes medications remained stable throughout the 22-week trial, the drop in A1c was considerably greater with a low-fat, vegan diet, compared to a diet following American Diabetes Association guidelines (-1.2 vs 0.4 percentage points, P = 0.01). The reductions in body weight and LDL cholesterol were also greater on the vegan diet.42
A low-fat, plant-based diet influences nutrient intake and body composition in several ways that may, in turn, affect insulin sensitivity:
First, because such diets are low in fat and high in fiber, they typically cause covert reductions in energy density and energy intake, which are not fully compensated for by increased food intake.43-45 The addition of 14 g of dietary fiber per day is associated with a 10% decrease in energy intake.44 As a result, low-fat, vegan diets are associated with significant weight loss,46 an important effect given that increased body fat, especially visceral fat, is associated with insulin resistance.47
Independent of their effect on body weight, reductions in total fat intake and in the proportion of dietary saturated fat to unsaturated fat increase insulin sensitivity.48 Increased carbohydrate intake is associated with increased insulin sensitivity in healthy individuals and with improved glycemic control and reduced cardiovascular risk factors in individuals with type 2 diabetes.41,49,50
Carbohydrate type may influence glucose control. A review of 5 studies of individuals with type 1 or type 2 diabetes showed that diets with lower glycemic indices significantly reduced A1c concentrations.51 Furthermore, diets richer in fiber tend to produce lower postprandial blood glucose concentrations, compared with fiber-depleted diets, and high-fiber diets have been shown to improve glycemic control in individuals with type 2 diabetes.52 Because vegan diets consist solely of plant-derived foods, they are typically high in fiber, compared with nonvegan diets,53 provided the diet does not rely heavily on processed foods.
Finally, limited evidence suggests that elevated body iron stores are associated with insulin resistance, while reductions in iron stores by any means (eg, dietary alterations or phlebotomy) increase insulin sensitivity.54 A vegan diet provides iron in its non-heme form, which is somewhat less absorbable than heme iron. A study comparing 30 ovolactovegetarians and 30 meat eaters, all of whom were healthy and had BMIs < 23 kg/m2, showed that the vegetarians had adequate, but lower, body iron stores, compared with the meat eaters: serum ferritin concentration 35 µg/l (95% CI, 21-49) versus 72 µg/l (95% CI, 45-100). The vegetarians also demonstrated less insulin resistance than the meat eaters: steady-state plasma glucose concentration 4.1 mmol/l (95% CI, 3.5-5.0) versus 6.9 mmol/l (95% CI, 5.2-7.5).54
Similar dietary changes are helpful for patients with type 1 diabetes. A high-fiber diet results in lower insulin requirements and improved management of blood glucose and lipids.55 The ability of plant-based diets to reduce cardiovascular risk factors is likely to be important in type 1 diabetes as well.
Further study is needed to establish optimal dietary interventions in gestational diabetes. Some evidence suggests that a diet limiting carbohydrates to 40% of calories, with fat providing 40% and protein providing the remaining 20%, improves glycemic control and reduces the need for exogenous insulin.56 Calorie allowance, if used, should be based on prepregnancy percentage of ideal body weight. Breakfast should be small because of the normal hypercortisolemic morning state in pregnancy, which opposes insulin and raises blood glucose concentrations. Future studies are required to compare a carbohydrate-reduced diet with a low-fat, high-fiber diet, particularly a vegan diet.
Because dietary change must be lifelong in diabetes, as in many other medical conditions, dietary adherence is a clinical challenge. Researchers have long lamented the poor adherence achieved with typical diets for diabetes.57 A potential weakness of such diets is that they require portion size limits for overweight persons, and limits on saturated fat intake are based on these limited energy intakes. As a result, individuals who exceed their prescribed energy intake limits with outsized portions can easily exceed recommended limits on saturated fat.
In this respect, vegan diets may present a clinical advantage. Because they include no animal fat, variations in food quantity are less likely to result in substantial increases in saturated fat intake. While vegetarian or vegan diets may sound restrictive, their acceptability in clinical studies is similar to that of seemingly more moderate therapeutic diets.58-61 Because vegan diets are based on the elimination of certain foods, they require no specified limits on portions, calories, or carbohydrates, and may be simpler to understand than regimens that limit quantities of certain foods without proscribing any.
Alcohol has mixed effects. Moderate alcohol intake (15-30 g of alcohol, equal to1-2 drinks/day) improves insulin sensitivity and is associated with a lower risk for type 2 diabetes.62,63 However, the association of alcohol intake with these purported benefits has not been proven in controlled clinical trials, and alcohol consumption is not without risks. Higher intakes (> 30 g/day) are associated with significantly increased risk for diabetes.63 For individuals treated with insulin or sulfonylureas, alcohol can increase the risk of hypoglycemia. In addition to potentially increasing breast cancer risk and potentially causing hazardous interactions with medications, alcoholic beverages consumed at mealtime can impair a patient's resolve to follow a healthful diet. Therefore, alcohol consumption should be discussed with a physician in individuals at risk for type 2 diabetes.
Dietary Supplements in Type 2 Diabetes
Several supplements have been investigated for their role in diabetes management, notably chromium and certain botanicals:
Chromium. The role of chromium as an insulin cofactor was discovered relatively recently.64 In 1977, Canadian researchers described the case of a woman in her mid-30s who received nutrition parenterally, as a result of prior intestinal surgery. Gradually worsening weight loss, hyperglycemia, and neuropathic symptoms led her doctors to institute treatment with increasing insulin doses. Eventually, the addition of chromium to her feeding regimen permitted discontinuance of insulin and marked symptomatic improvement.65
Until recently, the mechanism whereby chromium may improve indices of glucose metabolism was unknown. Current evidence indicates that this mineral works by increasing the presence of the main insulin-responsive glucose transporter (GLUT4) to the plasma membrane66 and by enhancing tyrosine phosphorylation of the insulin receptor.67
Dietary Reference Intakes (DRI) for micronutrients do not take into account the increased need for certain nutrients caused by certain diseases, including diabetes. Plasma levels of chromium have been found to be 25% to 30% lower in diabetic persons with mild or severe hypoglycemia than in euglycemic individuals.68
Although correcting chromium deficiencies is essential for blood glucose control, it is not yet clear that additional chromium helps. Randomized trials in individuals with type 1, type 2, or gestational diabetes, including trials using daily doses as high as 1,000 mcg, have yielded mixed results.69-71 As a result, most diabetes authorities do not recommend chromium supplements.
According to the Food and Nutrition Board of the Institute of Medicine, the safe and adequate daily intakes of chromium for adults 19 to 50 years of age are 35 mcg for men and 25 mcg for women. For people over 50, the numbers are 30 mcg for men and 20 mcg for women. Most common multiple vitamins include chromium, usually in amounts ranging from 100 to 200 mcg.
Botanicals. The role of certain botanicals for patients with type 2 diabetes is also under investigation. Metformin, for example, was developed from Galega officinalis (French lilac).72 The production of nitric oxide (important in signaling glucose uptake in skeletal muscle) is increased by American ginseng,73 which has been found in small studies to lower postprandial glucose in both diabetic and nondiabetic individuals.74 Bitter melon (Momordica charantia), a botanical with insulin-mimetic and gluconeogenesis-inhibiting effects, has also demonstrated blood glucose-lowering effects in humans.75
In spite of these initial benefits, problems remain with the use of botanicals in diabetes. First, clinical trials of ginseng and bitter melon have included only small numbers of persons, and confirmation of their blood sugar-lowering effects requires larger studies. Another problem is the lack of standardization of active ingredients, resulting in varying clinical effects.76
A low-fat, nondairy vegetarian (vegan) diet may be preferable for patients with diabetes. A low-glycemic-index diet provides additional benefits. A diet following ADA guidelines may also be considered.
Pregnant patients should work closely with a dietitian to ensure adequate nutrient intake.
Nutrition consultation is essential for advising patient in above dietary recommendations and arranging follow-up.
Exercise prescription, individualized.
What to Tell the Family
Some evidence suggests that dietary measures (breast-feeding and avoiding early introduction of dairy and gluten in infant diets) may lower the risk of type 1 diabetes. Further studies are necessary to evaluate this possibility. Type 2 diabetes and most cases of gestational diabetes are partly preventable through maintenance of healthy weight, regular exercise, and a healthy diet. In established disease, prevention of complications is possible through various diets, exercise, self-monitoring of blood glucose, and use of appropriate oral medication and/or insulin. Families can help prevent and more effectively manage diabetes by following similar dietary recommendations.
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