Type 2 Diabetes in Children

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3. Diabetes mellitus type 2 Is a metabolic disorder that is primarily characterized by insulin resistance, relative insulin deficiency & hyperglycemia It is rapidly increasing in the developed world Has characterized the increase as an epidemic Unlike type 1 diabetes, there is little tendency toward ketoacidosis in Type 2 diabetes, though it is not unknown Complex and multi-factorial metabolic changes lead to damage & function impairment of many organs, most importantly the cardiovascular system

4. Criteria for the Diagnosis of Diabetes Symptoms of diabetes plus random plasma glucose concentration ? 200 mg/dl (11.1 mmol/l). The classic symptoms of diabetes include: polyuria, polydepsia, and unexplained weight loss. OR FPG ? 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h. OR 2-h PG ? 200 mg/dl (11.1 mmol/l) during OGTT The test should be performed as described by W HO using a glucose load containing equivalent of 75-g anhydrous glucose dissolved in water.

5. Pathophysiology Insulin resistance means that body cells do not respond appropriately when insulin is present Other important contributing factors: increased hepatic glucose production (e.g., from glycogen degradation), especially at inappropriate times decreased insulin-mediated glucose transport in (primarily) muscles & adipose tissues (receptor and post-receptor defects) impaired beta-cell function—loss of early phase of insulin release in response to hyperglycemic stimuli

8. Underlying causes of type 2 diabetes

10. Obesity & Type 2 Diabetes

12. Too large meals ! Too high Calories !

13. Sedentary life style!!

19. The progressive nature of type 2 diabetes

21. Type 2 Diabetes in Children Clinical presentation Children with type 2 diabetes are usually diagnosed over age of 10 years Middle to late puberty Milder symptoms than type 1 with mild polydepsia, polyuria, little or no weight loss Glucosuria with / without ketonuria Up to 33% have ketonuria at diagnosis 5–25% of patients with type 2 diabetes have ketoacidosis at presentation

22. Associated problems with type 2 DM Obesity Insulin resistance Hyperinsulinism Arterial hypertension Hyperlipidemia Acanthosis Nigerians Macro & microangiopathy PCOS

23. Acanthosis Nigricans Acanthosis nigricans is a cutaneous finding frequently in darker-skinned obese individuals Characterized by velvety hyperpigmented patches most prominent in intertriginous areas and is present in as many as 90% of children with type II diabetes

24. Screening for type 2 DM in Children & Adolescents

25.  Why to screen for type 2 DM? As in adults, a substantantial number of children with type 2 can be detected in A symptomatic state In type 2, there is a prolonged latency period without symptoms during which abnormality can be detected Only children at risk for the presence or development of type 2 should be screened

26.  Criteria of screening for Type 2 DM in Children & Adolescents  overweight which is defined as (WHO) body mass index (BMI) > 85th percentile for age and sex weight for height > 85th % ile weight >120th % ile of ideal (50%) for height Plus two of the following risk factors: Family history of type 2 DM in first or second-degree relative

27.  Criteria of screening for Type 2 DM in Children & Adolescents  Race/ethnicity (Pima Indian, African-American, Hispanic,  Asian / Pacific Islander) Signs of insulin resistance or conditions associated with insulin resistance acanthosis nigricans polycystic ovary syndrome hypertension dyslipidemia

28. Type 2 diabetes is NOT a mild disease

33. Prevention of type 2 DM

34. Prevention of obesity

35. Prevention of type 2 DM Public health measures 1. Media 2. School 3. Community 4. Family Increase physical activity Reduce caloric intake/obesity Decrease sedentary life style I. Computer 2. Video games 3. Television

36. Treatment of type 2 diabetes There are limited data available regarding management of type 2 diabetes in children As a result, the goals of treatment in type 2 diabetes in adults have been applied to children and adolescents These goals include: achieving psychological & physical well-being long term glycemic control defined as a fasting plasma glucose < 130mg/dL HbA1c < 7% preventing microvascular & macrovascular complications

37. Initial treatment of type 2 DM, will vary depending on clinical presentation Wide range from A symptomatic hyperglycemia to DKA Children who are not ill at diagnosis can be managed with diet ,exercise & oral agents Children who are ill, dehydrated, presence of ketosis and acidosis need insulin therapy When stabilized, tapering of insulin gradually and introduction oral agents In all patients, identification & treatment of co-morbid conditions are important

38. How can insulin resistance be managed? Improve insulin resistance through: Diet Exercise Pharmacological intervention with agents that target insulin resistance

39. Oral hypoglycemic agents Biguanides: Metformin The first oral agent used should be metformin. decrease hepatic glucose output enhance hepatic & muscle insulin sensitivity without a direct effect on b-cell function Sulfonylureas: chlorpropamide, gliclazide, glimepiride, glipizide, tolazamide, & tolbutamide promote insulin secretion from islet cells Thiazolidenediones: troglitazone, rosiglitazone improve peripheral insulin sensitivity Troglitazone has been associated with fatal hepatic failure; its use in children is not recommended

40. Metformin The first oral agent should be used in type 2 Metformin has advantage over sulfonylureas of a similar reduction in HbA1c without the risk of hypoglycemia Metformin normalizes ovulatory abnormalities in girls with PCOS Because of concerns about lactic acidosis, Metformin is contraindicated in patients with: impaired renal function should be discontinued with the administration of  radiocontrast material. should not be used in patients with known hepatic disease, hypoxemic conditions, severe infections, or alcohol abuse

41. Metformin The most common side effects of Metformin Gastrointestinal disturbances Because proper dosing in children has not been evaluated & because most patients are near or at adult weight, it is reasonable to use the doses recommended for adults If monotherapy with Metformin is not successful over a period of time (3–6 months), Some clinicians would add a sulfonylurea, whereas others might add insulin

42. Sulfonylureas stimulate insulin secretion and reduce HbA1c levels by 1–2% Sulfonylureas may cause weight gain and are associated with the highest incidence of hypoglycemia among the oral antidiabetic agents. Glucosidase inhibitors slow the hydrolysis of complex carbohydrates and carbohydrate absorption (acarbose and miglitol) The glucosidase inhibitors reduce HbA1c by 0.5–0.9%

43. The thiazolidinediones improve peripheral insulin sensitivity & reduce HbA1c by 0.5–1.5% The thiazolidinediones do not cause hypoglycemia when used as monotherapy, but may cause edema & weight gain The sulfonylureas, nonsulfonylureas, glucosidase inhibitors & thiazolidinediones have not received approval by FDA for use in the pediatric population