Diabetes mellitus Yvona Pospíšilová Department of Internal Medicine, Hematology and Oncology FN Brno and Masaryk University Brno pospisilova.yvona@fnbrno.cz 2-3/2022 • • •The most frequent metabolic disease • •Relative or absolute insufficiency of insulin • •Hyperglycaemia • • •The most frequent cause of blidness • •The most frequent cause of amputation of lower extremities • •40 % patients on chronic dialysis • • lZimmet,P.: Preventing type 2 diabetes and dysmetabolic syndrome in the real word: a realistic view, Diabetic Medicine, 20, 2003 Classification of Diabetes • • •Type 1 diabetes mellitus • •Type 2 diabetes mellitus • •Gestational diabetes mellitus • •Specific types of diabetes due to other causes Other specific types • • •Genetic defects •Disease of the exocrine pancreas •Endocrinopathies •Infections • • •Drug – or chemical – induced diabetes (glucocorticoids) •Uncomon forms •Type 1 DM •- an absolute insulin deficiency • •a) immune-mediated (95%) • •b) idiopathic (mostly African or Asian ancestry) •Type 2 DM •- a relative insulin deficiency • •a) predominantly insulin resistance (Latinos) • •b) predominantly an insulin secretory defect (East Asians) • Type 1 Diabetes mellitus •6 % of all diabetics •mostly immune-mediated (autimmune destruction of beta-cells - insulitis) – in 96% •presence of antibodies: anti-GAD (glutamic acid decarboxylase), anti IA-2 (tyrosine phosphatase), antibodies to islet cells •strong HLA associations with DQA and DQB genes • •low C-peptide levels •low genetic predisposition (probability: 5 % in DM1 women, 8 % in DM1 men) • • • • • • • • • • •C-peptid •part of proinsulin •its concentration tells us about the amount of production of insulin C:\Users\25624\Pictures\300px-Cpeptid.png Risk factors – Type 1 DM • • • •Respiratory viruses ? •Enteroviruses ? • •Casein of cow milk ? • • Type 2 Diabetes mellitus • •94 % of all diabetics • heterogenous and multigenous • monogenous only in a very small percent •+ changes in life-style („coca - colonization“, „pandemic“) •strong genetic predisposition (probability: one parent – 50 %, both parents – 100 %) Diabetes mellitus typ 2 •a) insulin resistance (muscle, liver, fat) •b) an insulin secretory defect •c) progressively declining of beta-cell mass - declining of function of pancreas) • •GIT: incretin deficiency and/or resistance •Pancreas: hyperglucagonemia •Kidneys: enhanced glucose reabsorption •CNS: insulin resistance • Risk Factors – Type 2 DM • • •strong familial aggregation •age •obesity •physical inactivity •racial and ethnic subgroups (Native American, Polynesian, Micronesian, Asian-Indian, Hispanic, Afro-American) Diagnosis of DM • • • •fasting plasma glucose level (FPG) - 7,0 mmol/l or more •2 – hour postload plasma glucose level or casual plasma glucose level - 11,1 mmol/l or more • •without clinical symptoms - 2x • •Oral Glucose Tolerance Test (oGTT) - Czech •75 g glucose load, usually dissolved in water • • • Glycosylated/glycated haemoglobin (HbA1C) • • • •fusion glucose + haemoglobin (….compensation of DM for last 6- 8 weeks..) • •in some countries – dg of DM (only adult populations 6.5 % and more - by DCCT – US, Europe: 48 mmol/mol and more …) • •in every countries – compensation of DM Prediabetes….. • • • • • •microvascular complications - 7 mmol/l (fasting) •macrovascular complications - 6 mmol/l (fasting) Prediabetes („people with high risk of developing diabetes“) • • •1) Impaired glucose tolerance (IGT) • •7,8 – 11,0 mmol/l postprandial (2-hour postload) • • •independent risk factor for ischemic heart disease • • •2) Impaired fasting glucose (IFG) • •5,6 - 6,9 mmol/l fasting • • • • •3) Glyk. Hb 5.7-6.4 % (USA)…39-47 mmol/mol in Europe • Symptomatology of Type 1 Diabetes • • • • •beginning is quick (hours, dayes) •thirst, increasing urination, fatigue •hyperglycaemia, ketoacidosis, thirst, fatigue, coma…. Symptomatology of Type 2 Diabetes • • • •very often without any problems (many years…) •finding the comlications (skin, kidney, eyes, neuropathy..) • •can be thirst, increasing urination, fatigue •hyperglycaemia, mostly without ketoacidosis Screening for Type 2 DM and prediabetes • • •In all adults who are overweight (BMI 25 kg/m2 or more) and have additional risk factors in any time: •physical inactivity, first-degree relative with diabetes, members of high-risk ethnic population, women with GDM or PCOS or who delivered a baby weighing more than 9 lb (?), subjects with IGT or/and IFG, subjects with hypertension, dyslipidemia or history of CVD Screening for Type 2 DM and prediabetes • • • •In the absence of these criteria, testing should begin at age 40 (30…35?) years • •Testing should be repeated at 1-3 years intervals GDM (Gestational diabetes mellitus) – in Czech • • •In the first three months • at every pregnant women – normal fasting plasma glucose level (FPG) - less than 5,0 mmol/l • fasting plasma glucose level (FPG) 5,1-6,9 mmol/l – GDM • fasting plasma glucose level (FPG) ≥ 7 mmol/l or HbA1c ≥ 48 mmol/mol - DM •- No clear result → oGTT • GDM (Gestational diabetes mellitus) • • •In 24-28 week of pregnancy •at every woman oGTT •(dg: •fasting plasma glucose level (FPG) •5,1 mmol/l and more •after 1. hour - 10,0 mmol/l and more •after 2. hour - 8,5 mmol/l and more) • Long therapy with glucocorticoids - drug or chemical – induced diabetes (glucocorticoids) • • •there are problems with regulation of glucose in all patients • •almost 25 % (4-44 %) patients develop DM • •there is worsening of glucose in diabetics • • • • •level of glycaemia starts to increase 4-6 hours after application of glucocorticoids and lasts about 12 hours •the highest levels of glucose are in the afternoon and in the evening •the lowest levels of glucose are during the night and in the morning • • Drug – or chemical – induced diabetes (glucocorticoids) PS-PP IHOK glycemia 8.00 12.00 14.00 18.00 6.00 •Increasing of previous medications •Insulin – the highest levels in the noon, the lowest in the night….. • •Short acting insulin: 6 IU – 12 IU – 4 IU • • •The high levels of glucose should continue several dayes after termination of therapy with glucocorticoids • • • Treatment of patients with Diabetes Mellitus •Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach (Position Statement of ADA and EASD): Inzucchi, Bergenstal, Buse et all., in Diabetes Care, April 2012 • •„within the context of the needs, preferences, and tolerances of each patient, •individualization of treatment is the corneston of success“ •„the synthesis of best available evidence from the literature with the clinician´s expertise and patient´s own inclinations“ Treatment of Type 1 Diabetes • • •Insulin • •Insulin •(+ amylin agonist (pramlintid-inhibition of glucagon secretion and slowing gastric emtying) – in USA •p.o. antidiabetics – „do not work“ - Europe • •Transplantation (pancreas, pankreatic islets) Treatment of Type 2 Diabetes • • •1) Non – pharmacological ( life style intervention) • • •2) Pharmacological (drugs, insulin) • •3) „Surgery“ – gastric and intestine operation (gastric banding…) • Vasodilators Diuretics Central a-2 agonists ACEIs CCBs Peripheral a-1 blockers ß-blockers Adrenergic neuronal blockers ARBs 1 SUs Insulin Biguanides GLP-1 agonists Amylin analogues DPP-4 inhibitors Biguanides AGIs TZDs Meglitinides Adapted from: Inzucchi SE in Clinical Diabetes, Fonseca VA ed., 2006. SGLT2 inhibitors Antidiabetics 2 3 4 5 6 7 8 9 Treatment of Type 2 Diabetes • •Biguanides (metformin) • • - the main drug for treatment Type 2 DM • - reduces hepatic glucose output and reduces hepatic insulin resistance • - rarely if ever causes hypoglycemia • • Prediabetes and metformin • • • •BMI > 35 kg/m2 •Aged < 60 years •Women with prior GDM Metformin – systemic effects •decreasing of cancers •pozitive cardiovascular effect •stimulation of immunity response •anabolic effect on bone •pozitive effect on ovulation (PCOSy) •reduction of weight and waist circumferrence •pozitive effect on steatosis hepatis •decreasing of chronnic inflammatory process in a body •increasing activity of GLP-1 •hypolipidemic acivity •decreasing aggregability of trombocytes Treatment of Type 2 Diabetes • •Sulphonylureas • • - stimulate insulin secretion from beta cells of pankreas – exhaustion of pancreas • - can cause severe hypoglycemia • •There are not often used now…. • • • Treatment of Type 2 Diabetes • •Thiazolidinediones • • - reduce peripheral insulin resistance • - preserve residual function of beta-cells • - can cause heart insufficiency • (only pioglitazon is used….) • • „Incretin effect“… •…the insulin response to oral glucose is greater than for i.v. glucose • •Incretins (intestinal hormones) - GLP-1 (glucagon-like peptid): •stimulates insulin release from beta-cells •without hypoglycaemia •slowes gastric emptying (decreases glucose excursion and feeling of hunger) •centrally reduces food intake •promotes beta cell survival and their regeneration • • Treatment of Type 2 Diabetes • • •Incretin mimetics and enhancers: • •GLP-1 (glucagon-like peptid - 1) – receptor agonists • •DPP-4 inhibitors (inhibitors of dipeptidyl peptidase-4 – inhibition of enzyme which degrades GLP-1) • • • Treatment of Type 2 Diabetes • •Gliflozins – inhibition of reabsorbtion of glucose from kidney (SGLT2-inhibitors) • • - decreasing of increase reabsorbtion of glucose from kidney – DM Type 2 • - decreasing of glycaemia, blood pressure and weight • •New information: improvement kidney and heart insufficiency also in non–diabetic people!! • - Insulin • •essential in Type 1 DM (and GDM) • •Type 2 DM: •- glucose plasma level more than 15 mmol/l - decompensation of DM •- acidosis •- other serious diseases •- poor compensation of diabetes •- as a second step?? Type of insulin • • •Short (acting) human insulin (Regular) • •Rapid (acting) insulin analogues • •Intermediate (acting) human insulin (NPH) • •Long (acting) insulin analogues C:\Documents and Settings\25624\Dokumenty\Obrázky\350px-Insulin_short-intermediate-long_acting_svg.png • F1 Treatment of DM type 2 • • • •1) life style intervention + metformin (only highly motivated patients with glyk. Hb near target at diagnosis could be without farmacotherapy for 3-6 month) •2) + insulin • + sulphonylureas • + thiazolidindiones • + incretins •+ SGLT2-inhibitor •3) combinations of the above • Treatment of DM type 2 – 2021 (EASD + ADA): • • • •Add SGLT2 – inhibitors (gliflozins) to patients with heart (or kidney) insufficiency from the beginning….. • •ESC 2021 - + empagliflozin – in non-diabetic persons with heart failure with + also without reduction of EF Compensation • • •FPG („fasting“ plasma glucose) • •PPG („postprandial“ plasma glucose) • •Glycosylated/glycated haemoglobin (HBA1C) • New information in the past years…. • • •1) good compensation of diabetes at the beginning of the disease leads to less complications afterwards („glycemic memory“) • •2) there are more deaths when we try to have a good compensation of diabetes in patients with long duration of diabetes Glycemic targets • • • •Glycosylated/glycated haemoglobin (HbA1C) up to 45 mmol/mol at the beginning of the disease, long life expectancy, no CVD • •Glycosylated/glycated haemoglobin (HbA1C) up to 60 mmol/mol in people with complications of diabetes, e. g. severe hypoglycemia • •(Glycosylated/glycated haemoglobin more than 53 mmol/mol (7 % DCCT) – revise therapy) • • • •Blood pressure •Lipids •Antiplatelet treatment (??) •Retinopathy screening •Micro and macroalbuminuria and function of kidney screening •Neuropathy screening •Foot care Parametr Kompenzace výborná Kompenzace uspokojivá Kompenzace u pac. s vysokým KV rizikem Glykémie nalačno (mmol/l ) 4,0-6,0 6,0-7,0 < 7,0-8,0 Glykémie za 1-2 hod po jídle ( mmol/l ) 5,0-7,5 7,5-9,0 < 9,0 HbA1c - glykovaný hemoglobin mmol/mol < 45 45 - 54 54-60 Celkový cholesterol ( mmol/l ) do 4,5? HDL - cholesterol ( mmol/l) >1,1 LDL - cholesterol ( mmol/l ) 2,5 – 1,8 1,4 - 1,8 Triglyceridy ( mmol/l ) < 1,7 Krevní tlak ( mm Hg) < 130/80 < do 140/90 Hmotnostní index BMI ( body mass index ) (kg/ m2 ) muži 21 - 25 25 - 27 Hmotnostní index BMI ( body mass index ) (kg/ m2 ) ženy 20 - 24 24 - 26 Acute complications •acute life threatening - coma • •HYPOGLYCAEMIA • •HYPERGLYCAEMIA: 1.Hyperglycaemic ketoacidotic coma 2.Hyperglycaemic hyperosmolary coma 3.Laktacidotic coma • Glukagon GlukaGen Hypo KIT Glukagon BAQSIMI – glukagon powder (talc) – Elli-Lilly – from 7/2020 v ČR 640x0_0_3e28218b-baqsimi-photo-768x719 Powder…talc…. Specific chronic complications • 1. 1. 1.Diabetic nephropathy 2.Diabetic retinopathy 3.Diabetic polyneuropathy 4.„Diabetic foot“ (neuropathy + vascular disease) 5.Diabetic osteoartropathy Measurement of blood glucose • • •SMBG (Self Monitoring Blood Glucose) • •CGM (Continual Glucose Monitoring) • •FGM (Flash Glucose Monitoring) SMBG CGM FGM C:\Users\25624\Desktop\how-to-use%20-1.png C:\Users\25624\Desktop\how-to-use%20-2.png C:\Users\25624\Desktop\how-to-use%20-3.png Prevention of Type 1 DM • • • •Insulin •Nikotinamid •Imunosupresive therapy (cyclosporin) • •But none of these exactly works…….. • • • Prevention of Type 2 DM • • •Life style intervention • •Alfa-glucosidase inhibitors -acarbose •Metformin •Thiazolidinediones •Orlistat Prevention/delay of type 2 DM lPrisant, L.M.:Preventing Type II Diabetes Mellitus. J. Clin. Pharmacol, 44, 2004 FINDRISC (FINnish Diabetes RIsk SCore) 1.JPG 2.JPG C:\Users\25624\Desktop\Fota na papír 2016\IMG_6655.JPG Děkuji vám za pozornost