Diabetes mellitus. Treatment

Transcription

1 Diabetes mellitus Treatment

2 Recommended glycemic targets for the clinical management of diabetes(ada) Fasting glycemia: mg/dl Postprandial : mg/dl HbA1c: < 6,5 % Total cholesterol: < 200 mg/dl Triglyceride : < 150 mg/dl BP< 130 / 80 mm Hg (120 / 70 mm Hg) BMI < 25 kg/m 2 (M); < 24 kg/m 2 (F)

3 Dietary fat intake in diabetes Management (ADA 2010) Saturated fat intake should be 7% of total calories. (A) Reducing intake of trans fat lowers LDL cholesterol and increases HDL cholesterol (A); therefore, intake of trans fat should be minimized. (E) Carbohydrate intake in diabetes management In type 1 DM: 6 meals/day; CH- 20%(B)-10%- 30%(L)- 10%-20%(D)-10% In type 2 DM: 5 meals/day Monitoring carbohydrate, whether by carbohydrate counting, exchanges, or experience-based estimation, remains a key strategy in achieving glycemic control. For individuals with diabetes, the use of the glycemic index and glycemic load may provide a modest additional benefit for glycemic control over that observed when total carbohydrate is considered alone

4 Bariatric surgery (ADA 2010) Bariatric surgery should be considered for adults with BMI 35 kg/m2 and type 2 diabetes, especially if the diabetes or associated comorbidities are difficult to control with lifestyle and pharmacologic therapy. (B) Patients with type 2 diabetes who have undergone bariatric surgery need lifelong lifestyle support and medical monitoring. Physical activity People with diabetes should be advised to perform at least 150 min/week of moderate-intensity aerobic physical activity (50 70% of maximum heart rate). (A) In the absence of contraindications, people with type 2 diabetes should be encouraged to perform resistance trening three times per week. (A)

5 Insulin Action (h) Max. act(h) Duration INTENSIVE MANAGEMENT OF TYPE 1 DIABETES Rapid acting analogues Lispro L-aspart Glulisine 0,25 1,5 2-3h Regular insulin: Actrapid Humulin R Insuman Rapid Intermediary-acting: Insulatard Humulin NPH Insuman basal 30 2h 6-8 1h h Long acting analogues: Glargine,Detemir

6 INTENSIVE MANAGEMENT OF TYPE 1 DIABETES Premixed : Insulin MIXTARD 30 HUMULIN M3 INSUMAN Comb25;50 Analogues: NovoMix30 Humalog Mix25;50

7 INSULIN REGIMENS ONCE-DAILY INJECTION: LONG-ACTING ANALOGUE GLARGINE, DETEMIR TWICE-DAILY INSULIN INJECTIONS: 2 NPH or 2 PREMIXED INSULINS or 2PREMIXED RAPID ANALOGUE AND INTERMEDIATE INSULIN MULTIPLE DAILY INSULIN INJECTIONS: THREE INJECTIONS : 2 short-acting and 1 premixed insulin or 2 premixed-insulin and 1 short acting insulin(meal-time) FOUR INJECTIONS: 3 short-acting or rapid analogue and long acting analogue(bed-time)

8 INSULIN REGIMENS

9 INSULIN REGIMENS

10 Medical treatment in type 2 diabetes

11 Reasons for morning hyperglycemia SÖMÖGYI phenomenon: hyper after hypo DAWN phenomenon: early morning insulin resistance due toexcesive releasing of cortisol and GH

12 Primary sites of action of oral antidiabetic agents -glucosidase inhibitors Sulfonylureas/ meglitinides Biguanides Thiazolidinediones Carbohydrate breakdown/ absorption Insulin secretion Glucose output Insulin resistance Insulin resistance Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl. 1):S32 S40. Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13:

13 BIGUANIDES Mechanism of action: Decreasing hepatic glucose production by diminishing glicogenolysis and gluconeogenesis; Improves glucose utilization in skeletal muscles and adipose tissue by increasing cell membrane glucose transport.this effect may be due to improved binding of insulin to insulin receptors Decreased intestinal glucose absorbtion Insulin-sensitizing effects Decresing in plasma FFA, triglycerides and cholesterol levels Contraindications/cautions: Hepatic disease, cardiac failure Renal failure with blood creatinine >1,4 mg%, pregnancy and lactation Type 1 Diabetes, alcoholism, severe infections, shock Temporary: surgical interventions, X -ray procedures involving intravenous radiographic contrast agents

14 SULPHONYLUREAS Mechanism of action: Stimulation of ATP-dependent K-channels in pancreatic islet cells K-channels are closing and opening voltage-dependent Ca2+ channels, leadind to an intracellular increased Ca2+concentration Ca2+binds to calmodulin, resulting in exocitosis of insulin containing secretory granules.

15 SuIfonylureas Sulfonylurea glucose K ATP channels closed K + Ca 2+ Depolarization Insulin delivery Ca 2+ Ashcroft, Gribble, Diabetologia (1999) 42:

16 Name First generation Tolbutamid Clorpropamid Second generation Gliclazid Gliclazid MR Glipizid Gliquidona Glibenclamid MR Third Glimepirid SULPHONYLUREAS Duration of action(h) ,3-1, ,5-3,3 Daily dose(mg) Excretion Urine Urine , ,5-20 1,75-10,5 Biliary and urinary excretion Renal and biliary excretion Biliary 95% Renal and biliary excretion Renal 40% Biliary 60% MEGLITINIDES: -repaglinide 0,5-1-2 mg; daily dose=3 tb/day -nateglinide

17 THIAZOLIDINEDIONES Pioglitazone Mechanism of action: Agonists of PPAR(peroxizome proliferator- activated receptor).they stimulate transcription of some genes: GLUT 1 and GLUT 4,glukokinase, fosfoenolpiruvatcarboxikinase(pepck), fosfodiesterase, lipoproteinlipase,tnf-α, Insulin receptor TZD effects: Insulin-sensitizing effects Reduction in lipid plasmatic levels:reducing FFA availability, decreasing hepatic triglycerides synthesis and enhances peripheral clearance Enhance hepatic utilization of glucose Stimulates fat accumulation in the subcutaneous tissue rather than in visceral tissue. Decrease PAI-1 levels, platelet aggregation and proliferation in vascular smooth muscle cells from media to the intima.

18 α-glucosidase INHIBITORS Acarbose Miglitol Voglibose Mechanism of action: Potent inhibitors of the α-glucosidase enzymes present in the brush border of the enterocytes located in the proximal portion of the small intestine Inhibit glycoamylase,,sucrase,maltase,dextranase Delayes intraluminal production of monosaccharides and post-prandial rises of plasma glucose Effects: Improves insulin sensitivity Weight loss Decreasing in triglyceride levels Contraindications: Inflammatory bowel disease Colonic ulceration Predisposition to GI obstruction GI malabsorption or digestion

19 GLP-1 ANALOGUES

20 DPP-4 inhibitors

21 ADA/EASD MANAGEMENT GUIDELINE

22 High waist circumference Plus any two of Triglycerides ( 1.7 mmol/l [150 mg/dl]) HDL cholesterol Men < 1.0 mmol/l (40 mg/dl) Women < 1.3 mmol/l (50 mg/dl) Blood pressure 130 / 85 mm Hg FPG ( 5.6 mmol/l [100 mg/dl]), or diabetes METABOLIC SYNDROME Alberti KGM Lancet 2006