Personalized Prevention and Management of Diabetes
Diabetes is a rising global burden. This noncommunicable disease is a major global public health priority that is placing untenable demands on individuals, their careers, society, and their health system as a whole. This is informative speech outline diabetes disease in which the topic is discussed.
Estimates from a 2017 count show that there is a global rise of 425 million people with the disease with these numbers are expected to rise in 2045 to 629 million. This disease is spurred on by the global rise in obesity and unhealthy habits including poor diets and lack of physical activity. These are made worse by societal determinants, including changes in nutrition in a global context. The classification of diabetes separates it into two main types, Type 1 and Type 2, with Type 2 diabetes accounting for a majority, almost 85%, of the total diabetic population. Both forms of diabetes can lead to multisystem health issues including retinopathy, nephropathy and neuropathy. This also includes ischemic heart disease, stroke and peripheral vascular disease.
Types of Diabetes
The etiology of Type 1 diabetes is not one that is understood. The exact cause of Type 1 diabetes is unknown. Usually, the body's own immune system — which normally fights harmful bacteria and viruses — mistakenly destroys the insulin-producing cells in the pancreas. It is a chronic condition in which the pancreas produces little or no insulin. Insulin is a hormone needed to allow sugar (glucose) to enter cells to produce energy. Different factors, genetics- possibly viruses, may add to Type 1 diabetes. Although Type 1 diabetes usually manifests during childhood or adolescence, it can develop in adults. Despite active research, Type 1 diabetes has no cure. Treatment focuses on managing blood sugar levels with insulin, diet, and lifestyle to prevent complications. These symptoms may occur suddenly.
Type 2 diabetes is more well understood. The modifiable factors in the causation of Type 2 diabetes are better known, making prevention a realistic public health goal. Type 2 diabetes results from the body’s ineffective use of insulin. Type 2 diabetes comprises most people with diabetes around the world and is largely the result of excess body weight and physical inactivity. Symptoms may be like those of Type 1 diabetes but are often less marked. As a result, the disease may be diagnosed several years after onset, once complications have already arisen. Until recently, this type of diabetes was seen only in adults, but it is now also occurring increasingly frequently in children.
The epidemiology of diabetes shows distinct patterns of distribution by age, sex, ethnic group and rural or urban area of residence; this varies markedly between Type 1 and type 2 diabetes. Genetic and behavioral risk factors, and the interplay between them, are important in the etiology of diabetes. Progress has been made in understanding the modifiable factors in the etiology of Type 2 diabetes, which has opened opportunities for prevention.
Geographical Variation
International Diabetes Federation estimates from 2017 indicate that >96,000 new cases of type 1 diabetes are diagnosed globally per year in children and adolescents aged Variation with age, sex and ethnicity: Type 1 diabetes can occur at any age but is rare in the first year of life. In most populations, the incidence steadily increases with age up to puberty, and is higher among those aged 35 years. Overall, there is a male excess among young adults. Among children, there is a slight male excess in high-incidence countries, while the opposite is seen in low-incidence countries, but the differences are small. Mirroring the geographical pattern, the incidence is higher in populations of European origin than in non-Europeans.
Temporal Variation
The incidence of type 1 diabetes has been rising, with average increases of around 3.0% per year worldwide. The relative magnitude of increase is generally greater in low-incidence countries. The most pronounced increase is in the youngest age group (0–4 years). The incidence of type 1 diabetes also varies with season, being highest in autumn and winter.
Etiological Factors
Genetic susceptibility is important but not enough in the causation of type 1 diabetes. Environmental factors have a more important role in progression from islet autoimmunity to overt disease, possibly because improved living standards have reduced exposure to microorganisms, leading to increased autoimmunity. Despite research efforts, no single environmental factor has been proven to be causally related to type 1 diabetes. However, associations have been described or hypothesized for early social mixing, viral infections, vaccinations, drugs, toxins, intrauterine factors, and dietary and nutritional factors such as exclusive breastfeeding and delayed introduction of cow's milk. Vitamin D deficiency has been implicated by some observational and genetics studies, and a role of omega-3 fatty acids has also been suggested.
Type 2 diabetes
The slow onset of type 2 diabetes, and its usual presentation without the acute metabolic disturbance seen in type 1 diabetes, means that the true time of onset is difficult to determine. There is usually a long (3–7-year) pre-detection period during which glucose levels are elevated but often not diagnosed clinically. Depending on the setting, a substantial proportion of the total number of cases in a population at a given time may be undiagnosed. Globally, approximately half (50%) of the people aged 20–79 years with diabetes are unaware of their disease, though this proportion varies by world region and opportunities for systematic or opportunistic screening, ranging between a third undiagnosed overall in high-income countries, to more than 75% undiagnosed in low-income countries.
Diagnosis of type 2 diabetes
Because the ratio of detected to undetected cases can vary by population and over time, epidemiological research aimed at defining the true prevalence of type 2 diabetes has relied on studies in which the presence and absence of disease are defined by a biochemical test for blood glucose level. Diagnostic criteria were previously limited to the use of blood glucose measures during a 75 g oral glucose tolerance test, with the World Health Organization (WHO) defining diabetes as a fasting glucose ≥7.0 mmol/liter and/or a 2-hour post–challenge glucose of ≥11.1 mmol/liter.
The WHO and other agencies such as the American Diabetes Association have recently also approved the use of glycated hemoglobin (HbA1c) for the diagnosis of diabetes, with a cut-off of 48 mmol/mol (6.5%). This test has the benefit of not requiring a fasted sample, but the availability of standardized laboratories and the cost are considerations in some contexts. The interpretation of HbA1c test results should take account of anemia, renal impairment and, for some HbA1c tests, haemoglobinopathies. Whatever method is used to diagnose diabetes clinically, the diagnosis should be confirmed with repeat testing using the same method.
Variation in prevalence by geographical location, ethnicity, age and sex: Around 425 million people worldwide (approximately 9% of adults aged 20–79 years) were estimated to have diabetes in 2017. Figure 2 shows the age-standardized prevalence of type 2 diabetes and impaired glucose tolerance. As in type 1 diabetes, there is marked geographical variation, but the pattern is different. The prevalence is lowest in rural areas of developing countries, generally intermediate in developed countries, and highest in certain ethnic groups, particularly those that have adopted Western lifestyle patterns. Populations with the highest prevalence have a high prevalence of obesity.
It is hypothesized that genetic susceptibility to obesity would be disadvantageous in times of food abundance, but advantageous when food is scarce, driving its persistence by natural selection. This ‘thrifty genotype’ hypothesis is supported by evidence of gene–environment interaction: individuals who migrate from low-prevalence areas to developed countries have an increased risk of type 2 diabetes. For instance, type 2 diabetes is up to 4- to 6-fold more prevalent in immigrant South Asians and African-Caribbean individuals in the UK compared with white European populations. There is a small sex difference in the global numbers of people with diabetes, with about 17 million more men than women estimated to have diabetes in 2017. The prevalence increases sharply with age in both sexes.
Incidence and temporal variation: The annual incidence is approximately 6.7–7 per 1000 per year in developed countries, when ascertained by self-report (USA data) or studies using serial glucose tolerance testing. The incidence in individuals known to have IGT is about 10-fold greater than in those with normal glucose tolerance. The risk of future progression to diabetes is also greater in those with other hyperglycemic states, including gestational diabetes mellitus. US data show a near 5-fold increase of diagnosed diabetes, from 5.5 million persons in 1980 to 23.4 million in 2015. This increase mirrors the increasing prevalence of obesity. Worldwide, there is a projected increase in the prevalence of diabetes in adults from 425 million (8.8%) in 2017 to 629 million (10.1%) in 2045. Estimates of prevalence in developing countries show even more marked increases, particularly in areas where populations are rapidly adopting Western lifestyles.
The increase in prevalence of obesity in childhood has led to the appearance of type 2 diabetes in children and young adults, particularly those in highly susceptible ethnic groups. US data show an average annual increase in incidence of type 2 diabetes among youth (age 10–19 years) of 4.8% over 2002–2012, but the annual rate of increase in incidence was markedly higher among youth of Native American (8.9%), black (6.3%), Hispanic (3.1%) and Asian or Pacific islander (8.5%) origin compared with white youth (0.6%).
Etiological factors
The main pathophysiological defects leading to type 2 diabetes are insulin resistance and a relative insulin secretory defect. The main etiological risk factors are age, obesity, family history, ethnicity, physical inactivity and diet. Much progress has been made in understanding dietary risk factors, particularly the critical importance of overall dietary quality: the risk-raising impact of diets characterized by high consumption of red and processed meat, sugar-sweetened beverages and refined carbohydrate sources; the risk-reducing impact of fruit and vegetables; some types of dairy products such as yoghurt; and overall healthy eating patterns including higher sources of foods rich in polyunsaturated fats, fiber and whole-grain products, legumes and nuts.3 Novel strategies to use nutritional biomarkers in tissues such as blood, which supplement information from self-report dietary assessment methods, are paving the way for a more detailed understanding of the association between diet and diabetes. The role of wider societal determinants, including nutrition transition in a global context, is also now recognized as a key driver of dietary intakes.
Although the heritability of type 2 diabetes is high (30–70%) and >400 genetic variants related to diabetes risk have now been identified,4 the individual effects of genetic variants are modest; even when combined into a genetic score, known genes contribute little to prediction of diabetes. Phenotype-based risk models provide greater discrimination for diabetes. The current conclusion is that genetic variants provide important insights into the biological pathways and pathogenesis of diabetes, but not its prediction. It is likely that interactions between behavioral and genetic factors provide an explanation for the risk of type 2 diabetes but demonstrating such an interaction is challenging.
Primary prevention
Randomized clinical trials in several countries have provided evidence that, in high-risk individuals with IGT, progression to type 2 diabetes can be reduced by intensive lifestyle intervention with diet or physical activity, or with drug therapy using glucose-lowering agents such as metformin. In addition to their clinical effectiveness, there is now also evidence for the cost-effectiveness of these interventions. The challenges that remain are to determine how high-risk individuals should be identified, and how lifestyle changes in terms of healthier diet and regular physical activity can be sustained in real-world settings.
As in many areas of primary prevention, high-risk approaches can be effective for the individuals included in the programmed but have a limited impact on the public health burden of diabetes. Complementary approaches that seek to make small shifts in the population distribution of dietary and physical activity behaviors are required. Such approaches make relatively little difference to risk at the individual level but have a major impact on the public health burden of diabetes when that risk reduction is summated across large numbers of people in the population. The future challenge involves finding ways of integrating high-risk and population approaches to prevention and balancing relative investment in the two strategies.
Secondary prevention: screening
Screening for type 2 diabetes was proposed in the hope that early detection and treatment would reduce long-term burden. This was tested for cardiovascular outcomes among individuals with screen-detected diabetes in ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care), a primary care-based trial of intensive multifactorial treatment compared with routine care. This trial has shown the following: that screening for diabetes is feasible, with little short- or long-term adverse psychological impact; that cardiovascular risk factors (blood pressure, cholesterol, smoking, weight) improve after screen detection of diabetes, even among those being given routine general practice care; but that, at the population level, invitation of high-risk individuals to screening is not associated with a reduction in all-cause or diabetes-related mortality over 10 years.5
Uncertainties remain concerning optimal strategies to increase uptake of screening, deliver care to screen-detected patients and manage those who screen negative but are at high risk of diabetes and cardiovascular disease; the overall cost-effectiveness of screening programmed is also uncertain. Rather than screening whole populations for diabetes, primary care teams should focus efforts on earlier detection, lifestyle advice and intensive treatment of risk factors among individuals at high risk of diabetes and cardiovascular disease. In some settings, such as the UK, this is offered within the vascular health check programmed in primary care.
New horizons
To conlude informative speech on diabetes outline, there is continuing interest in opportunities for the personalized prevention and management of diabetes. Whether such personalization will best be achieved through genetic or phenotypic approaches, or a combination, is the subject of ongoing research. Further refinement of the classification of type 2 diabetes into heterogeneous subgroups has also been proposed as a strategy to help differentiate people with differing disease progression trajectories.
