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Type 2 diabetes mellitus is the predominant form of diabetes worldwide, accounting for 90% of cases globally. An epidemic of T2DM is under way in both developed and developing countries, although the brunt of the disorder is felt disproportionately in non-European populations. In the Pacific island of Nauru, diabetes was virtually unknown 50 years ago and is now present in approximately 40% of adults. The IDF estimated in 2014 that 387 million people have diabetes worldwide and that by 2035 this number will rise to 592 million. Of those with diabetes currently, 77% live in low- and middle-income countries and 179 million are undiagnosed. These estimates are substantially greater than predicted even a decade ago, suggesting that the global epidemic is still progressing. In the United States, the Centers for Disease Control and Prevention (CDC) estimated in 2014 that 29.1 million people, or the 1 last update 07 Jul 2020 9.3% of the population, had diabetes and that 8.1 million of them (27.8%) were undiagnosed. In 2012, they estimated based on fasting glucose or hemoglobin A_1c levels that 86 million people (37% of adults over age 20) had prediabetes and thus were at high risk of developing diabetes.^1-4Type 2 diabetes mellitus is the predominant form of diabetes worldwide, accounting for 90% of cases globally. An epidemic of T2DM is under way in both developed and developing countries, although the brunt of the disorder is felt disproportionately in non-European populations. In the Pacific island of Nauru, diabetes was virtually unknown 50 years ago and is now present in approximately 40% of adults. The IDF estimated in 2014 that 387 million people have diabetes worldwide and that by 2035 this number will rise to 592 million. Of those with diabetes currently, 77% live in low- and middle-income countries and 179 million are undiagnosed. These estimates are substantially greater than predicted even a decade ago, suggesting that the global epidemic is still progressing. In the United States, the Centers for Disease Control and Prevention (CDC) estimated in 2014 that 29.1 million people, or 9.3% of the population, had diabetes and that 8.1 million of them (27.8%) were undiagnosed. In 2012, they estimated based on fasting glucose or hemoglobin A_1c levels that 86 million people (37% of adults over age 20) had prediabetes and thus were at high risk of developing diabetes.^1-4

The economic burden of diabetes is enormous. The IDF estimates that in 2014 diabetes-related health expenditures amounted to 11% of total health spending on adults.reverses diabetes type 2 can drink alcohol (☑ hands) | reverses diabetes type 2 foot painhow to reverses diabetes type 2 for the 1 last update 07 Jul 2020 ³³ The CDC suggests that diabetes costs in the United States were $245 billion with average expenditures per person, adjusted for age and gender, 2.3-fold higher than in the nondiabetic population. for 1 last update 07 Jul 2020 ⁴⁴ The increases in cost are driven by complications, comorbid conditions, and increasing complexity of care driving prescription costs and the frequency of visits.⁵

Considerable information is available on the factors that are responsible for the development of T2DM, and these determinants are summarized in Table for 1 last update 07 Jul 2020 31-1Table 31-1.¹ T2DM is thought to occur in genetically predisposed persons who are exposed to a series of environmental influences that precipitate the onset of clinical disease. The genetic basis of T2DM is discussed in detail later in this chapter, but the syndrome consists of monogenic and polygenic forms that can be differentiated both on clinical grounds and in terms of the genes that are involved in the pathogenesis of these disorders. Sex, age, and ethnic background are important factors in determining the risk of developing T2DM. The disorder is more common in women, and the increased prevalence in certain racial and ethnic groups has already been alluded to. Age is also a critical factor. T2DM has been viewed in the past as a disorder of aging, and this remains true today. However, the prevalence of obesity and T2DM in children has risen dramatically. In the past, it was believed that the overwhelming majority of children with diabetes had type 1 diabetes mellitus (T1DM), and only 1% to 2% of diabetic children were considered to have T2DM or other rare forms of diabetes. More recent reports suggest that as many as 20% to 25% of children in the United States with newly diagnosed diabetes have non–immune-mediated forms of the disease. Most of these children have T2DM, but other types are being increasingly identified. Nevertheless, T2DM in children remains relatively rare, with an estimated prevalence of 5 cases per 10,000 children.^4,6

Epidemiology

Systematic screening for asymptomatic type 2 diabetes mellitus is generally limited to high-risk populations, rendering broader prevalence estimates imprecise. Total U.S. prevalence is now estimated at 8%, but probably exceeds 25% in persons older than 65 years. Type 2 diabetes is more common in Native Americans, Hispanic Americans, and African Americans, in whom the prevalence exceeds 12 to 13%, than in whites,; these patients also typically present at an earlier age. Prevalence rates vary worldwide; type 2 diabetes has a propensity for Asiatic Indians, Polynesians-Micronesians, and Latin Americans. Interestingly, African blacks, Australian Aborigines, Asians, and Pacific Islanders all have an increased risk for diabetes after emigration to the United States; this may be attributable to a genetically determined inability to adapt metabolically to “Western” behavior patterns (i.e., reduced physical activity and a high-fat, high-calorie diet).

Although relatively little is known about the specific genetic abnormalities associated with type 2 diabetes, the personal factors promoting disease expression are well established. Increased age, reduced physical activity, and obesity are risk factors for the disease, especially in genetically susceptible persons. The severity and duration of obesity contribute significantly to diabetes risk; patients with high waist-to-hip ratios (i.e., central or upper body obesity) are also more prone to the disease. Family history is also important because type 2 diabetes occurs more frequently in persons with diabetic parents or siblings. Identical twin concordance rates approach 100%; in these cases, affected twins will even often develop diabetes at a similar age.

Epidemiology

Systematic screening for asymptomatic type 2 diabetes mellitus is generally limited to high-risk populations, rendering broader prevalence estimates imprecise. Total U.S. prevalence is now estimated at 8%, but probably exceeds 25% in persons older than 65 years. Type 2 diabetes is more common in Native Americans, Hispanic Americans, and African Americans, in whom the prevalence exceeds 12 to 13%, than in whites,; these patients also typically present at an earlier age. Prevalence rates vary worldwide; type 2 diabetes has a propensity for Asiatic Indians, Polynesians-Micronesians, and Latin Americans. Interestingly, African blacks, Australian Aborigines, Asians, and Pacific Islanders all have an increased risk for diabetes after emigration to the United States; this may be attributable to a genetically determined inability to adapt metabolically to “Western” behavior patterns (i.e., reduced physical activity and a high-fat, high-calorie diet).

Although relatively little is known about the specific genetic abnormalities associated with type 2 diabetes, the personal factors promoting disease expression are well established. Increased age, reduced physical activity, and obesity are risk factors for the disease, especially in genetically susceptible persons. The severity and duration of obesity contribute significantly to diabetes risk; patients with high waist-to-hip ratios (i.e., central or upper body obesity) are also more prone to the disease. Family history is also important because type 2 diabetes occurs more frequently in persons with diabetic parents or siblings. Identical twin concordance rates approach 100%; in these cases, affected twins will even often develop diabetes at a similar age.

Abstract

Antipsychotics are associated with an increased risk of type 2 diabetes mellitus (T2DM). T2DM affects around 10% of people receiving antipsychotics. The consequences of T2DM in this population include increased rates of micro- and macrovascular complications, acute metabolic decompensation, and premature mortality. Multiple complex mechanisms underlie the association between T2DM and antipsychotic medication use. A causative link between antipsychotics and T2DM appears to exist. The general approach to T2DM prevention and management should be similar to those for the general population, but enhanced for this high-risk population. Lifestyle interventions are integral in order to reduce incident T2DM. In addition, improved uptake of opportunities to screen for T2DM will reduce the prevalence of undiagnosed diabetes. Currently people receiving antipsychotics receive poorer treatment for T2DM than the general population. Consequently, health-care professionals in primary care, diabetes services, and mental health-care teams have a responsibility to ensure that people receiving antipsychotics are not disadvantaged.

Race and ethnicity

Type 2 diabetes is overrepresented among racial and ethnic minority groups in the United States. In the United States, the highest incidence of type 2 diabetes is among Native Americans followed by Non-Hispanic blacks and Hispanics; Non-Hispanic whites have the lowest incidence of youth onset type 2 diabetes.³¹ In a case series of pediatric hyperglycemic hyperosmolar syndrome, African American males with type 2 diabetes comprised two-thirds of patients with HHS.¹² Keep in mind that type 2 diabetes can present in all ethnic groups, and still accounts for almost 15% of all youth onset diabetes cases among non-Hispanic whites.³¹ The landscape of type 2 diabetes is not the same worldwide. For instance, in some Asian countries, there are different phenotypes of type 2 diabetes, of which some occur in nonobese children.³⁶

Introduction

Type 2 diabetes is characterized by a relative disparity between endogenous insulin production and insulin requirements, leading to an elevated blood glucose. The primary pathogenetic lesion in type 2 diabetes has yet to be discovered. Primary insulin resistance of the peripheral tissues has been suggested by many as the initial event. Similarly, insulin secretion abnormalities have been argued as the primary defect in type 2 diabetes. It is likely that both phenomena are important in the development of type 2 diabetes, and genetic defects predisposing to both are likely to be important contributors to the disease process. GWAS in recent years appear to suggest that failure of insulin secretion is the key event that initiates type 2 diabetes.

7.6 Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is the most common form of diabetes mellitus and accounts for over 90% of all cases. It was formerly referred to as non-insulin-dependent diabetes mellitus. Type 2 diabetes mellitus is adult onset, is characterized by insulin resistance, and may also be accompanied by beta cell dysfunction causing insulin deficiency. Many patients with type 2 diabetes mellitus are obese because obesity itself can cause insulin resistance. However, these patients may not need insulin initially after diagnosis or even throughout their life. Timely diagnosis of type 2 diabetes mellitus is important because early intervention can prevent many complications of type 2 diabetes mellitus (including neuropathy, nephropathy, and retinopathy), but such diagnosis is often difficult because hyperglycemia develops gradually and at an early stage a patient may not notice any classical symptoms of diabetes. Ketoacidosis seldom occurs in type 2 diabetes, and, when seen, it is usually associated with a stress factor such as infection.

SLC30A8: type 2 diabetes

Type 2 diabetes refers to the common form of non-insulin-dependent diabetes mellitus and is not an autoimmune disorder. Patients with type 2 diabetes have detectable levels of insulin in circulation, but they do not need insulin to prevent ketoacidosis. Although the genetic correlation for the susceptibility to type 2 diabetes is not specified, the SLC30A8 gene is thought to be associated with an increased risk of the development of type 2 diabetes. The SLC30A8 gene is selectively expressed in pancreatic beta cells and encodes a zinc transporter, ZnT-8. The protein is associated with insulin secretion in the human pancreas (Chimienti et al., 2005). The transporter is localized on the membrane of intracellular vesicles and accumulates zinc from the cytoplasm into intracellular insulin-containing compartments. Mutations of the SLC30A8 gene result in impaired pancreatic beta cell function leading to defects in insulin secretion that confer susceptibility to diabetes mellitus.

Publisher Summary

Type 2 diabetes has become a significant global health care problem. Hypertension is also a very common and well-established risk factor for cardiovascular morbidity and mortality. Based on accumulating evidence from animal and human studies, suboptimal vitamin D status has emerged as a probable risk factor for both type 2 diabetes and hypertension and vitamin D supplementation has been suggested as a potential intervention to prevent type 2 diabetes and hypertension. The results seen in the observational studies are supported by biological plausibility, and raise the possibility that optimizing vitamin D status may have a role in reducing risk of type 2 diabetes and hypertension. Type 2 diabetes and hypertension are multifactorial diseases and it is unlikely that vitamin D deficiency would prove to be a central cause or a major therapeutic target; nevertheless, it is imperative that randomized trials are conducted in well-defined populations (e.g., pre-diabetes, early diabetes, pre-hypertension, whites versus non-whites) to test the hypothesis that vitamin D is a direct contributor to the pathogenesis of type 2 diabetes and hypertension and has a role in prevention or therapy.