Diabetes Mellitus

Diabetes, Global scenario, Indian Scenario, Types, Prevention and Control

1. DIABETES MELLITUS

2. Introduction Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Insulin is a hormone that regulates blood sugar. Hyperglycaemia, or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, especially the nerves and blood vessels.

3. Health impact Over time, diabetes can damage the heart, blood vessels, eyes, kidneys, and nerves. Adults with diabetes have a two- to three-fold increased risk of heart attacks and strokes. Combined with reduced blood flow, neuropathy (nerve damage) in the feet increases the chance of foot ulcers, infection and eventual need for limb amputation. Diabetic retinopathy is an important cause of blindness, and occurs as a result of long-term accumulated damage to the small blood vessels in the retina. Diabetes is the cause of 2.6% of global blindness. Diabetes is among the leading causes of kidney failure.

4. Types of diabetes Type of diabetes Brief description Type 1 diabetes β- cell destruction (mostly immune-mediated) and absolute insulin deficiency; onset most common in childhood and early adulthood Type 2 diabetes Most common type, various degrees of β- cell dysfunction and insulin resistance; commonly associated with overweight and obesity Hybrid forms of diabetes Slowly evolving, immune-mediated diabetes of adults Similar to slowly evolving type 1 in adults but more often has features of the metabolic syndrome, a single GAD autoantibody and retains greater β- cell function Ketosis-prone type 2 diabetes Presents with ketosis and insulin deficiency but later does not require insulin; common episodes of ketosis, not immune-mediated WHO CLASSIFICATION OF DIABETES MELLITUS 2019

5. Types of diabetes Other specific types Brief description Monogenic diabetes - Monogenic defects of β- cell function - Monogenic defects in insulin action Caused by specific gene mutations, has several clinical manifestations requiring different treatment, some occurring in the neonatal period, others by early adulthood Caused by specific gene mutations; has features of severe insulin resistance without obesity; develops when β- cells do not compensate for insulin resistance Diseases of the exocrine pancreas Various conditions that affect the pancreas can result in hyperglycaemia (trauma, tumor , inflammation, etc.) Endocrine disorders Occurs in diseases with excess secretion of hormones that are insulin antagonists Drug- or chemical-induced Some medicines and chemicals impair insulin secretion or action, some can destroy β- cells Infection-related diabetes Some viruses have been associated with direct β- cell destruction Uncommon specific forms of immune-mediated diabetes Associated with rare immune-mediated diseases Other genetic syndromes sometimes associated with diabetes Many genetic disorders and chromosomal abnormalities increase the risk of diabetes Unclassified diabetes Used to describe diabetes that does not clearly fit into other categories. This category should be used temporarily when there is not a clear diagnostic category especially close to the time of diagnosis

6. TYPES OF DIABETES Hyperglycaemia first detected during pregnancy Diabetes mellitus in pregnancy Type 1 or type 2 diabetes first diagnosed during pregnancy Gestational diabetes mellitus Hyperglycaemia below diagnostic thresholds for diabetes in pregnancy Diagnostic criteria for diabetes: fasting plasma glucose ≥ 7.0 mmol /L or 2-hour post-load plasma glucose ≥ 11.1 mmol /L or Hba1c ≥ 48 mmol / mol Diagnostic criteria for gestational diabetes: fasting plasma glucose 5.1–6.9 mmol /L or 1-hour post-load plasma glucose ≥ 10.0 mmol /L or 2-hour post-load plasma glucose 8.5–11.0 mmol /L

7. Problem statement The number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. The global prevalence of diabetes* among adults over 18 years of age rose from 4.7% in 1980 to 8.5% in 2014. Between 2000 and 2016, there was a 5% increase in premature mortality from diabetes. Diabetes prevalence has been rising more rapidly in low- and middle-income countries than in high-income countries. Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation. In 2016, an estimated 1.6 million deaths were directly caused by diabetes. Another 2.2 million deaths were attributable to high blood glucose in 2012. Almost half of all deaths attributable to high blood glucose occur before the age of 70 years. WHO estimates that diabetes was the seventh leading cause of death in 2016. WHO GLOBAL REPORT ON DIABETES

8. Problem statement An estimated 463 million adults aged 20 –79 years are currently living with diabetes. This represents 9.3% of the world’s population in this age group. The total number is predicted to rise to 578 million (10.2%) by 2030 and to 700 million (10.9%) by 2045. The estimated number of adults aged 20–79 years with impaired glucose tolerance is 374 million (7.5% of the world population in this age group). This is predicted to rise to 454 million (8.0%) by 2030 and 548 million (8.6%) by 2045. An estimated 1.1 million children and adolescents (aged under 20 years) have type 1 diabetes. It is currently not possible to estimate the number of children and adolescents with type 2 diabetes. The number of deaths resulting from diabetes and its complications in 2019 is estimated to be 4.2 million. An estimated 15.8% (20.4 million) of live births are affected by hyperglycaemia in pregnancy in 2019. Annual global health expenditure on diabetes is estimated to be USD 760 billion. It is projected that expenditure will reach USD 825 billion by 2030 and USD 845 billion by 2045. INTERNATIONAL DIABETES FEDERATION ATLAS 2019

9. Problem statement WHO GLOBAL REPORT ON DIABETES WHO Region Prevalence (%) Number (millions) 1980 2014 1980 2014 African Region 3.1% 7.1% 4 25 Region of the Americas 5% 8.3% 18 62 Eastern Mediterranean Region 5.9% 13.7% 6 43 European Region 5.3% 7.3% 33 64 South-East Asia Region 4.1% 8.6% 17 96 Western Pacific Region 4.4% 8.4% 29 131 Total  4.7% 8.5% 108 422

10. Problem statement Diabetes prevalence in 2019 and projections to 2030 and 2045 (65–99 years) - INTERNATIONAL DIABETES FEDERATION ATLAS 2019

11. Problem statement Global diabetes estimates and projections – INTERNATIONAL DIABETES FEDERATION ATLAS 2019

12. Problem statement – India According to the World Health Organization (WHO): There are estimated 72.96 million cases of diabetes in adult population of India. The prevalence in urban areas ranges between 10.9%-14.2% and prevalence in rural India is at 3.0-7.8% ,among population aged 20 years and above with a much higher prevalence among individuals aged over 50 years. According to National Diabetes and Diabetic Retinopathy Survey report (2015-19): Prevalence of diabetes in India has been recorded at 11.8% in the last four years, prevalence of known diabetes cases was 8% and new diabetes cases at 3.8%. The prevalence of diabetes among males was 12%, whereas among females it was 11.7%. Highest prevalence of diabetes (13.2%) was observed in the 70-79 years’ age group.

13. Risk factors for diabetes If he/she is overweight (BMI is more than 23kg/m 2 ) If he/she is physically inactive, that is, he or she exercises less than 3 times a week If he/she has high blood pressure If he/she has impaired fasting glucose or impaired glucose tolerance If his/her triglyceride and/or cholesterol levels are higher than normal If his/her parents/siblings or grandparents have or had diabetes If she delivered a baby whose birth weight was 4 kgs or more If she has had diabetes or even mild elevation of blood sugars during pregnancy

14. When to suspect diabetes Symptoms of uncontrolled hyperglycemia : excess thirst, excess urination, excess hunger with loss of weight Frequent infections Non-healing wounds Unexplained lassitude Fatigue Impotence in men

15. Criteria for diagnosis of T2DM using venous blood samples Fasting Glucose (mg/dl) 2-hour Post-Glucose Load (mg/dl) Diabetes Mellitus >=126 or >=200 Impaired Glucose Tolerance < 126 and >140 to <200 Impaired Fasting Glucose >=110 to <126 *WHO Definition 1999 Capillary blood glucose value is also sufficient. Where capillary blood glucose measured by glucometer is used in the fed state (i.e., post food/post glucose/post meal), the >200 mg/dl cut off may be revised to >220 mg/dl.

16. Modified diagnostic criteria for diabetes Fasting is defined as no caloric intake for at least 8 hours. The 2-hour postprandial glucose test should be performed using a glucose load containing the equivalent of 75g anhydrous glucose dissolved in water. The American Diabetes Association (ADA)2 recommends diagnosing ‘prediabetes’ with HbA1c values between 39 and 47 mmol / mol (5.7–6.4%) and impaired fasting glucose when the fasting plasma glucose is between 5.6 and 6.9mmol/L (100–125mg/ dL ). INTERNATIONAL DIABETES FEDERATION ATLAS 2019

17. Impaired glucose tolerance and impaired fasting glucose Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are conditions of raised blood glucose levels above the normal range and below the recommended diabetes diagnostic threshold. The terms ‘prediabetes’, ‘non-diabetic hyperglycaemia’,  ‘intermediate hyperglycaemia’ are in use as alternatives. Glycosylated Haemoglobin (HbA1C) A fraction of hemoglobin in the RBCs is found to be in a glycosylated form i.e. has glucose attached to it. The HbA1c level is proportional to average blood glucose concentration over the previous two to three months and therefore is an excellent indicator of how well the patient has managed his/her diabetes over the last four weeks to three months. American Diabetes Association (ADA) recommends an HbA1c goal of less than 7% for people with diabetes in general

18. Initial assessment of diabetic patients History (Ask for) Physical Examination (Look for) Duration since onset of symptoms Body Mass Index Precipitating factors such as recent infections, stress, change in dietary habits or physical activity levels Waist circumference, Waist-hip ratio Acanthosis nigricans * Acanthosis nigricans * Hypertension, pre-existing cardiovascular Diseases Blood pressure Drug history Peripheral pulses Diet Feet: calluses, ulcers, prominent veins, edema , injuries Physical Activity: type, frequency Fundus examination Family History Cardiovascular system -Diabetes and complications -Age at onset -Cardiovascular disease, if any Peripheral nervous system Thyroid *Acanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin, usually present in the posterior and lateral folds of neck, axilla, groin, umbilicus, and other areas. This occur due to insulin spill over (from excessive production due to obesity or insulin resistance) into the skin which results in its abnormal growth, and the stimulation of colour producing cells.

19. Initial management Pharmacotherapy for the management of hyperglycemia and any other co-morbid conditions e.g. high blood pressure, dyslipidemia etc.; Therapeutic lifestyle management, and Diabetes patient Education and counselling

20. Principles of management The basic principles in the management of type-2 diabetes are: Modify Lifestyle: diet and physical activity. Reduce Insulin resistance through reduction in weight, specifically reduction of fat mass. Pharmacological treatment (if inadequate control): Metformin/ Sulfonylureas. Treatment for high blood pressure: ACE Inhibitors, Calcium channel blockers such as amlodipine and diuretics such as hydrochlorothiazide (For details refer the ppt on hypertension). Lipid control with statins.

21. Ideal targets of control in the management of diabetes Fasting Blood Glucose 115 mg/dl Post Meal Blood Glucose <160 mg/dl HbA1C <7% Total Cholesterol <180 mg/dl LDL-cholesterol <100 mg/dl HDL cholesterol <45 mg/dl Blood pressure <130/80 mg/dl Serum TG <150mg/dl Source: ICMR 2005 guidelines Note: The targets for diabetic population are lower than the non-diabetes

22. Non-pharmacological management of diabetes *Source: ICMR 2005 GUIDELINES Lifestyle Goals in Diabetes: To improve health through optimum nutrition To provide energy for reasonable body weight , normal growth and development To maintain glycemic control To achieve optimum blood lipid levels To individualise the diet according to complications and co-morbidities Achieve optimal physical activity Advise other behavioural changes for: smoking, other tobacco products and alcohol Advocate stress management

23. Non-pharmacological management of diabetes Medical Nutrition Therapy (MNT) for diabetes mellitus requires application of nutritional and behavioural sciences along with physical activity. We need a four-pronged approach: Nutritional assessment which includes metabolic, nutritional and life style parameters. Setting goals – practical, achievable and acceptable to the patient - individualised Nutritional Intervention, including nutrition education – individualized meal plans according to family eating patterns Evaluation – to assess if the goals have been achieved and to make necessary changes. *Source: ICMR 2005 GUIDELINES

24. Non-pharmacological management of diabetes Dietary Recommendations: Energy: Ideal Body Weight (IBW) = (Height in cm – 100) * 0.9. Approximately, 25 kcals/kg ideal body weight/day can be given to a moderately active patient with diabetes. Energy or Calorie Distribution: Carbohydrates: 55-60 % of energy from carbohydrates is an ideal recommendation Fibre recommendation for general population is 40 g/day (2000 Kcals) Proteins should provide 12-15 % of the total energy intake for people with diabetes Fats should provide 20-30 % of total energy intake for people with diabetes. *Source: ICMR 2005 GUIDELINES

25. Non-pharmacological management of diabetes Fat quality Saturated fats (SFA) ≤10% energy and 7% in those with raised blood lipid levels Polyunsaturated fats (PUFA) 10 % energy, n6: 3-7% energy, n3: >1% energy, n6/n3 ratio 5-10 Monounsaturated Fatty Acids (MUFA) 10-15% energy + any calories left from the carbohydrate portion Trans fats < 1% energy – preferably totally avoided Salt: Added (iodized) salt should be less than 5 g/day For persons with hypertension and diabetes, the intake should be reduced to less than 3 g/ day Alcohol: best to avoid, however if used, should be taken in moderation it should not be counted as part of the meal plan. alcohol does provide calories (7 kcal/ g), which are considered as “empty calories” In the fasting state, alcohol may produce hypoglycaemia *Source: ICMR 2005 GUIDELINES

26. Non-pharmacological management of diabetes Sweeteners: Nutritive Sweeteners: These include fructose, honey, corn syrup, molasses, fruit juice or fruit juice concentrates dextrose, maltose, mannitol, sorbitol and xylitol. All these are best avoided. Non-nutritive Sweeteners: Aspartame, acesulfame K, stevia, sucralose and saccharin are currently approved for use. However, they should be used in moderation and are best avoided in pregnancy. *Source: ICMR 2005 GUIDELINES

27. Non-pharmacological management of diabetes Physical Benefits of exercise: Improves insulin sensitivity, reduces the risk of heart disease, high blood pressure, bone diseases, and unhealthy weight gain Keeps one flexible and agile Helps relieve stress, anxiety and prevents depression Increases strength and stamina Promotes sound sleep Increases metabolic rate and digestion Delays the process of aging Activity and Exercise: Recommendation is about 150 minutes of aerobic activity or its equivalent /week along with some resistance training at least twice a week and flexibility exercises. Extra quick acting carbohydrate snack before the exercise and during the exercise, if the exercise period extends the daily-recommended routine. *Source: ICMR 2005 GUIDELINES

28. Healthy diet and physical activity WHO recommendations on physical activity are provided for different age groups It is recommended that children and youth aged 5–17 years should do at least 60 minutes of moderate- to vigorous-intensity physical activity daily. It is recommended that adults aged 18–64 years should do at least 150 minutes of moderate - intensity aerobic physical activity (for example brisk walking, jogging, gardening) spread throughout the week, or at least 75 minutes of vigorous-intensity aerobic physical activity throughout the week, or an equivalent combination of moderate- and vigorous-intensity activity. For older adults the same amount of physical activity is recommended, but should also include balance and muscle strengthening activity tailored to their ability and circumstances.

29. Pharmacological management of diabetes Oral anti-hyperglycaemic agents (OHA) Insulin therapy Non-insulin injectable therapy

30. Anti – hyperglycaemic drugs BIGUANIDES SULPHONYLUREAS DPP - 4 INHIBITORS Dipeptidyl peptidase-4 inhibitors (Gliptins) Metformin Metformin SR Glibenclamide Glipizide Glipizide modified release Gliclazide Gliclazide modified release Glimepiride Sitagliptin Vildagliptin Saxagliptin Linagliptin Teneligliptin Gemigliptin ALPHA GLUCOSIDASE INHIBITORS SGLT 2 INHIBITORS Sodium-glucose cotransporter-2 inhibitor NON-SULPHONYLUREA SECRETAGOGUES ( Glinides ) Acarbose Voglibose Miglitol Canagliflozin Dapagliflozin Empagliflozin Repaglinide Nateglinide

31. Insulin therapy Indications: Person with diabetes with significant symptomatic hyperglycaemia, loss of weight and polyuria, polydipsia, polyphagia Fasting plasma glucose > 270 mg/dl or HbA1c >9% Severe infections Presence of ketosis Other situations: Patients not responding to optimal doses of OHA alone or in combination. Acute hyperglycaemia, diabetic ketoacidosis/ hyperglycemic -hyperosmolar state/lactic acidosis. Stressful situations such as acute myocardial infarction, stroke, acute infections, tuberculosis, trauma and other conditions requiring hospitalisation Pregnancy and lactation Peri -operative state Intolerant/contraindications to OHA Hepatic and renal failure Renal transplantation Person with diabetes on steroids

32. Insulin therapy Types of insulin preparations: Human insulin Short acting – human soluble insulin (regular) Intermediate acting – neutral protamine Hagedorn (NPH) Premixed- mixtures of regular and NPH insulin in 25/75, 30/70, 50/50 proportion Insulin Analogues: Rapid acting (e.g. Lispro , Aspart , Glulisine ) Long acting (Glargine, Degludec , Detemir ) Premixed Insulin analogue ( Lispro / lispro protamine, aspart / aspart protamine) Co-formulations ( Degludec + Aspart insulin)

33. Non-insulin injectable therapy (GLP - 1 receptor agonists) GLP - 1 Receptor Agonists Exenatide Liraglutide Lixisenatide Dulaglutide

34. Complications of diabetes Acute complications: Hypoglycaemia Hyperglycaemic emergencies (Diabetic Ketoacidosis- DKA or Hyperosmolar Hyperglycaemic State - HHS) Chronic Complications: Serious organ damage involving eyes, heart, kidney, nerves and limbs, which ultimately can lead to blindness, heart attack, kidney failure and limb amputation respectively Coronary Artery Disease Diabetic Nephropathy Diabetic Retinopathy: Diabetic Neuropathy Diabetic Foot

35. When to refer to higher facility (CHC/SDH/DH) Uncontrolled infections Co-morbid conditions, e.g., Hypertension, CAD, COPD, CKD etc. Severe cellulitis Unresponsive UTI or other deep seated infections including bad diabetic foot needing intravenous antibiotics Recurrent UTI not responding to oral antibiotics Presence of ketones in urine

36. Foot care advice to the patients DO DO NOT Inspect feet daily using mirror Walk barefoot Wash feet daily in lukewarm water, also in between toes Do not Smoke/alcohol abuse Apply moisturizing lotion to feet after drying Expose to extreme temperature Have your feet checked at each clinic visit Use hot fomentation Inspect footwear daily for defects/foreign bodies Use chemicals agents (e.g. corn plaster), corn caps or blades to treat corns or calluses Change footwear regularly Wear new footwear for more than few hours Buy footwear preferably in the evening Neglect any minor foot lesions

37. WHO Voluntary Global Targets for Prevention and Control of Non-Communicable Diseases to be Attained by 2025

38. KEY MESSAGES Diabetes is a serious, long-term condition that occurs when the body cannot produce any or enough insulin or cannot effectively use the insulin it produces. The main categories of diabetes are type 1, type 2 and gestational diabetes mellitus. Type 1 diabetes is the major cause of diabetes in childhood but can occur at any age. At present, it cannot be prevented. People with type 1 diabetes can live healthy and fulfilling lives but only with the provision of an uninterrupted supply of insulin, education, support and blood glucose testing equipment. Type 2 diabetes accounts for the vast majority (around 90%) of diabetes worldwide. It can be effectively managed through education, support and adoption of healthy lifestyles, combined with medication as required. Evidence exists that type 2 diabetes can be prevented and there is accumulating evidence that remission of type 2 diabetes may be possible for some people.

39. KEY MESSAGES ‘Prediabetes’ is a term increasingly used for people with impaired glucose tolerance and/ or impaired fasting glucose. It signifies a risk of the future development of type 2 diabetes and diabetes-related complications. Pregnant women with gestational diabetes mellitus can have babies that are large for gestational age, increasing the risk of pregnancy and birth complications both for the mother and baby.

40. Diabetes control programme in India NATIONAL PROGRAMME FOR PREVENTION AND CONTROL OF CANCER, DIABETES, CARDIOVASCULAR DISEASES AND STROKE* *For details, refer to PPT on hypertension

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