![Diagnostic criteria
• Severe dehydration
• • Marked hyperglycaemia (plasma
glucose >30 mmol/L)
• • Serum osmolality >320 mosmol/kg
• Effective serum osmolality = 2 (Na2+)
[mmol/L] + glucose [mmol/]
• There is no significant ketonaemia (<3.0
mmol/L) or acidosis (pH >7.3, HCO3>15
mmol/L).](https://image.slidesharecdn.com/type2diabetesmellitust2dmpart3v2-250824041901-92115f44/85/Type-2-Diabetes-Mellitus-T2DM-Part-3-v2-pptx-49-320.jpg)
Type 2 Diabetes Mellitus (T2DM) Part 3 v2.pptx
- 1. Type 2 Diabetes Mellitus (T2DM) Part 3 •Primary Care Department •MAHSA University •2024/2025
- 2. Learning Outcomes At the end of this session students should be able to: 1. Discuss investigations in T2DM 2. Explain complications for T2DM and acute complication- HHS 3. Outline a holistic management (drugs and lifestyle modification) including comorbids
- 3. Aim of treatment The overall aims of management are to: • improve quality of life • reduce complications; and • prevent premature death.
- 4. Short-term & Long-term aims • Short-term • Relief of symptoms and acute complications • Long-term aims • Achievement of appropriate glycaemic levels with lifestyle management including weight reduction (where appropriate) and maintain durability of glycaemic control • Reduction of other CV risk factors • Identification and treatment of chronic complications • Optimise quality of life
- 5. Introduction • At diagnosis, • a detailed history, • full physical examination and • baseline investigations must be done to assess the cardiovascular disease risk factors and complications arising from diabetes. • Management (Mx) should be based on the initial clinical assessment and baseline investigations. • Mx involves • lifestyle modification, • medications and • patient education to promote self-care and empowerment. • Prior to increasing the dose or adding a new oral medication or insulin, compliance to therapy has to be determined satisfactorily.
- 6. Less stringent for • Elderly • With Comorbidities (coronary artery disease, heart failure, renal failure, liver dysfunction) • Short life expectancy • Prone to hypoglycaemia Adapted from : Ministry Of Health Malaysia. (2021). Clinical Practice Guidelines : Management of Type 2 Diabetes Mellitus (6th Edition ed.). Management Goals - follow up (target levels) In those who do not have pre-existing CHD, but have a higher risk of stroke and DKD, lower SBP target of <130 mmHg (but not <120 mmHg) might be appropriate provided that it is well tolerated, to lower the risk of stroke and albuminuria
- 7. Newly diagnosed is defined as T2DM <1-year duration and recently diagnosed is defined as T2DM duration of <5 years
- 11. Diabetic education • Should be offered in a timely manner • Suggested at four critical times • at diagnosis, • annually, • when complicating factors arise • when transitions in care occur.
- 12. Dietary & Lifestyle Modification 1. Realistic weight loss of 5-10 % of initial body weight over a 6-month period is beneficial for all overweight or obese patients who have or are at risk for diabetes. 2. Patients should monitor and limit their total caloric, carbohydrate & fat intake during each meal. 3. Exercise of moderate-intensity should be encouraged for at least 150 minutes per week 4. Smoking cessation
- 13. Medical Nutrition theraphy • preventing diabetes, managing existing diabetes, and delaying complication • Proper diet is crucial at all stages • an adjunct to it • Dietician-at diagnosis, sub-optimal metabolic and/or weight control, at initiation of insulin therapy, development of other co-morbidities • hyperlipidaemia, hypertension and DKD
- 14. Healthy diet • CHO intake should emphasize nutrient-dense CHO sources that are • high in fibre, including vegetables, fruits, legumes, whole grains, and dairy products • Protein- lean sources of protein such as lean meat, fish, chicken/poultry without skin and soy protein. • limit total fat intake,saturated fats and minimise trans- fat for prevention and treatment of CVD. • - A healthy diet -oats, nuts and legumes, green leafy vegetables and soy protein may be beneficial
- 15. Weight management in T2DM • Individuals who are • overweight (BMI >23.0 kg/m2 - <27.5 kg/m2) and • obese (>27.5 kg/m2) and • not achieving glycaemic control should restrict their caloric intake with the goal of reducing body weight by at least 5%-10%. • Structured lifestyle intervention and: - • Meal Replacement Plans (MRP) have been shown to be effective in lowering HbA1c, lipid profile and BP. • Total diet replacement (TRP) (≤800 kcal/day) inducing weight loss up to 15% (approximately 15 kg) from baseline has been shown to lead to diabetes remission in T2DM patients.
- 16. Protect the kidneys • Sodium – In normotensive and hypertensive patients – • reduced sodium intake (<2,000 mg sodium/day OR 5 g of salt a day OR 1 teaspoon) with • a diet high in fruits, vegetables, and • low-fat dairy products lowers BP
- 17. Exercise • insulin sensitivity of regular exercise training persists for up to 5 days after inactivity • The duration of exercise should be at least 150 minutes/week of moderate intensity or at least 75 minutes/week of vigorous aerobic physical activity and at least 2 sessions per week of resistance exercise • 60 minutes per day/approximately 450 minutes per week in overweight or obese patients to-weight reduction
- 18. Tobacco cessation • smoke have a higher risk for cardiovascular morbidity and premature mortality and worse glycaemic • control compared with T2DM non-smokers
- 20. Oral Anti-diabetic Agents(OGLDs) 1. Prescribe OHA if hyperglycemia is inadequately controlled with lifestyle modifications. 2. Metformin is first-line therapy for type 2 diabetes, unless contraindicated or not tolerated. 3. Evaluate every 3-6 months and adjust as needed to account for new patient factors and glycemic control. Some patients may dual/triple therapy based on their glycemic control. 4. In patients on dual/triple therapy with HbA1c above target, injectable therapy will be considered.
- 23. Oral Anti-diabetic Agents (OADs)/ OGLDs Groups of OADs 1. Biguanides ( Metformin)* 2. Sulfonylurea* 3. Meglitinides 4. Alpha-Glucosidase Inhibitors (AGIs)* 5. Thiazolidinedione/glitazones 6. Dipeptidyl peptidase IV/ (DPP-4) inhibitor 7. SGLT2 inhibitor Efficacy, hypoglycemic risk, impact on weight, potential side effects, cost, and patient preference will guide choice of pharmacologic agent *Available at most government primary care clinics
- 26. Metformin • MOA - decreases hepatic glucose production, decreases insulin resistance, decreases intestinal absorption of glucose • does not stimulate insulin secretion- no hypoglycaemia • Reduces HbA1c by 1.5%- at maximal dose of 2gm/day + healthy lifestyle • glycemic efficacy,very low incidence of hypoglycemia
- 27. Side effects of Metformin • nausea, anorexia and diarrhoea. • minimised if taken together with/or after meals. • To reduce gastrointestinal side effects, it is best to start with a single daily dose, followed by weekly titration or use Extended release formulation • Long term complications - vitamin B12 deficiency • Lactic acidosis is rare usually associated with renal impairment • Serum creatinine- 200 remove metformin • At serum creat-150- half the dose
- 28. Metformin • Use in combination with other OGLDs has a synergistic effect to further • reduce plasma glucose and may reduce insulin requirement • Safe in pregnancy and lactation
- 29. Sulphonylurea • increasing insulin secretion • average A1c reduction of 0.4-1.6% • Side effect- hypoglycaemia, weight gain • Second generation SU – gliclazide and glimepiride-less hypo and weight gain • Diamicron/ gliclazide MR • Glibenclamide/ Daonil • SUs should be taken 10-30 minutes before meals
- 30. 3. Alpha glucosidase inhibitors (acarbose) • Lowers postprandial glucose without causing hypoglycaemia • Side effect- GIT bloating, abdominal discomfort, diarrhoea and flatulence • Decreases HbA1c (05-1.4)%
- 31. Thiazolidinediones (TZDs)/glitazones • MOA - increasing insulin sensitivity in muscle, adipose tissue and liver • Side effects include weight gain (due to redistribution of body fat), fluid retention, heart failure, macular oedema and osteoporosis. • CI --in pts with CCF and liver failure
- 32. Incretin • The incretin effect is decreased in T2DM, results in delayed and • reduced insulin release an lack of suppression of glucagon release • after a meal • 2 classes of drugs increase the effect of incretins improve glucose control • A. DPP4-i(incretin enhancer) • B.GLP-1 analogue or GLP1-RA (incretin mimetic)
- 33. Dipeptidyl Peptidase-4 (DPP-4) Inhibitors/gliptins • lowers A1c by 0.5–0.8%, • combined with other OAD(s). • • It is weight neutral and has minimal risk of hypoglycaemia • No adverse CV outcome
- 34. Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors • selectively inhibits SGLT2, a transporter • reducing glucose reabsorption leading to an increase in urinary glucose excretion. • SGLT2 inhibitors in clinical development inhibit only 30–50% of the filtered glucose load • weight loss (2.5 to 3.0 kg) and modest blood pressure reduction • with lower risk of hypoglycaemia • SE- genitalia and urinary tract infection, increase in risk of DKA, volume depletion, osmotic diuresis • euglycemic diabetic ketoacidosis (eDKA) have been reported in patients on SGLT2-i with inter-current illness
- 35. Injectable Agents • Glucagon-like Peptide-1 (GLP-1) Receptor Agonists • side effects of all GLP1-RAs are gastro-intestinal i.e. nausea,vomiting and diarrhoea • GLP-1RAs have been shown to reduce HbA1C (~0.8-1.6%), body weight (~1.0-4.1 kg).. The weight reduction is due to the • effect on satiety and delay in gastric emptying • Insulin therapy
- 36. Insulin Therapy 1. Insulin therapy should be considered in the following situations • Inadequate glycaemic control on optimal dose and number of OADs • Short term use ( acute illness or surgery, pregnancy, Breast Feeding, DKA, HSS) • As initial therapy in newly diagnosed T2DM o Symptomatic (osmotic symptoms : polyuria, polydipsia, weight loss) regardless of A1c or FPG o A1c >10% or FPG >13 mmol/L 2. Intensification of treatment should not be delayed if patient is not achieving glycemic goals.
- 37. OGLDs • Agents that are known to improve fasting hyperglycaemia include metformin and TZDs while others reduce mainly postprandial hyperglycaemia • The medication regimen should be re-evaluated at regular intervals (3-6 • months) and adjusted as needed to incorporate new patient factors such as: • - ASCVD, • - heart failure, • - DKD, • - hypoglycaemia event, • - weight gain, • - cost concern; and
- 38. Clinical Monitoring Schedule ( √= must do, + = optional, - = omit )
- 39. Management of comorbidities • Statins are the drug of choice for lowering low- density lipoprotein cholesterol • Prescribe a statin for most adults > 40 years old with diabetes • Offer an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) in nonpregnant patients with hypertension or albuminuria
- 40. Others • Diabetes Education • Team Approach
- 41. Summary • Diabetes Education • Team Approach • Targets for Control • Lifestyle Modification • Diet • Weight Loss • Exercise • Medication • Oral Anti-diabetic Agents • Injectable Agents • Monitoring • Management of Comorbidities
- 42. SLEEP AND T2DM • T2DM) has been associated with higher incidence of slee p disorders • peripheral neuropathy, restless legs syndrome, periodic li mb movements, rapid changes in blood glucose levels du ring night leading to hypoglycemic and hyperglycemic episodes, nocturia and associated depression
- 43. Sleep disturbance causes t2dm • shorter sleep duration and erratic sleep behavior have been linked with higher incidence of obesity, metabolic syndrome, and T2DM
- 44. Sleep disturbance causes t2dm • Difficulty initiating sleep increased the risk of T2DM by 55%, • while difficulty maintaining sleep increased its risk by 74%. • the risk of developing T2DM associated with insufficient (≤5 h/day) or excessive sleep duration (≥9 h/day) or performing shift work was comparable to that of being physically inactive.
- 45. Diabetes and malignancies • An increased risk of different types of cancer with T2DM: • pancreatic, • liver, • breast, • colorectal, • urinary tract, • gastric, • female reproductive cancers
- 46. POSSIBLE BIOLOGIC LINKS BETWEEN DIABETES AND CANCER RISK • Hyperinsulinemia is a hallmark of insulin resistance • Hyperglycemia • Chronic inflammation-- increased levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein.
- 47. HHS • a life-threatening emergency • suspected in patients with T2DM who are very ill with significant hyperglycaemia. • • Can be an initial presentation of undiagnosed T2DM (7-17%). • • Diagnosis of HHS must be prompt and managed intensively in HDU • • The elderly with multiple co-morbidities are prone to HHS. • .
- 48. HHS • • It has a higher mortality than DKA and vascular complications such as MI,stroke or peripheral arterial thrombosis are common • Uncommon complications such as seizures, cerebral oedema and osmotic demyelination syndrome though due to rapid changes in osmolality during treatment • HHS progresses over many days. • As a result, the dehydration and metabolic disturbances are • more profound
- 49. Diagnostic criteria • Severe dehydration • • Marked hyperglycaemia (plasma glucose >30 mmol/L) • • Serum osmolality >320 mosmol/kg • Effective serum osmolality = 2 (Na2+) [mmol/L] + glucose [mmol/] • There is no significant ketonaemia (<3.0 mmol/L) or acidosis (pH >7.3, HCO3>15 mmol/L).
- 50. important clinical features • there is worsening of acute cognitive impairment, consider: • › cerebral oedema in severe cases or the presence of significant electrolyte disturbances, • › hyperosmolality (>330 mosmol/kg), • › sudden drop in osmolality, • › severe dehydration, infection and sepsis, • › hypoglycaemia during treatment; and • › renal failure.
- 51. Precipitating factors for HHS • › Infection (30-60%) • › Poor adherence to treatment – omission of insulin or OGLDs • › Presence of acute concomitant illness – cerebrovascular events, myocardial infarction • › Medication – diuretics, glucocorticoids or antipsychotic drugs
- 52. Management goals • gradual and safe: • › correction of dehydration, • › correction of electrolyte imbalance, • › control of hyperglycaemia, • › treatment of precipitating factors, • › prevention of complications
- 53. Mx • IV 0.9% saline solution is the principal fluid to restore circulating volume and correction of dehydration • Recognition of pseudohyponatremia in severe hyperglycaemia is important as to avoid using hypertonic saline • Aim for gradual reduction in serum osmolality at the rate of 3-8 mosm/kg/hr.
- 54. MX • Too rapid fall in glucose should be avoided • Aim for a reduction in blood glucose of 4-6 mmol/L/hr • Prophylactic low molecular weight heparin (LMWH) • Identify and treat the precipitating cause
- 55. Mx • Once HHS resolves, transition from IV insulin to SC basal bolus insulin. • However, patients with HHS are more insulin sensitive and may require lower insulin dose. • • To reduce the risk of recurrence and prevent long-term complications, • discharge planning should include: • diabetes education, dietitian referral, • education on medications including insulin administration, if required
- 56. References 1. Ministry Of Health Malaysia. (2021). Clinical Practice Guidelines : Management of Type 2 Diabetes Mellitus (th Edition ed.). 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628550/ sleep 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058741/ cancer
Editor's Notes
- #6: Glycaemic target should be individualized to minimize risk of hypoglycaemia *** HbA1c=6.5% is advocated for patients with a shorter duration of T2DM, no evidence of significant CVD and longer life expectancy and have minimal risk of hypoglycaemia. In individuals with established CVD, LDL-C target is 1.4 mmol/L (Refer Table 3-26: LDL-C targets)
- #13: nutrition-based treatment provided by a registered dietitian nutritionist. It includes “a nutrition diagnosis ,therapeutic and counseling services to help manage diabetes.” Is an intensive, focused, and comprehensive nutrition therapy service. Involves in-depth individualized nutrition assessment. Relies heavily on follow-up to provide repeated reinforcement to aid with behavior change. Establishes goals, a care plan, and interventions. Plans for follow-up over multiple visits to assist with behavioral and lifestyle changes relative to each individual’s nutrition problems and medical condition or disease The goals of MNT are to: › improve HbA1c, BP, cholesterol levels, achieve and maintain body weight A1c goals, › promote healthful eating patterns in appropriate portion sizes and limiting food choices only when supported by scientific evidence, › provide nutrition needs based on cultural preferences, health literacy and numeracy, willingness and ability to make behavioural changes .73
- #14: In normotensive and hypertensive patients, a reduced sodium intake (<2,000 mg sodium/day or 5 g of salt a day or 1 teaspoon) with a diet high in fruits, vegetables, and low-fat dairy products lowers BP
- #17: insulin-sensitising effect of an acute bout of exercise does not last beyond this Duration Elevated fasting plasma glucose in T2DM patients with dawn phenomenon, may be reduced by performing early morning exercise in the fasting state
- #23: The medication regimen should be re-evaluated at regular intervals (3-6months) and review patient factors: ASCVD, - heart failure, - DKD, - hypoglycaemia event, - weight gain,
- #26: generally well-tolerated with minimal side effects and is affordable. extracted from an herb rich in guanidine, Galega officinalis (‘goat’s rue’ or French lilac) increases glucose uptake by the skeletal muscle, reducing absorption of glucose from the intestines and inhibits hepatic glucose production (reducing gluconeogenesis and hepatic glycogenolysis metformin increases the plasma levels and gene expression of the two main intestinal hormones, GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), also known as ‘incretins’ (i.e. intestinal-derived hormones capable of modulating the endogenous secretion of insulin), and improving the ‘sensitivity’ to the ‘incretin’ effect, making itself a candidate as a GLP1 ‘enhancer’ and ‘sensitizer’ drug.
- #27: Agents that are known to improve fasting hyperglycaemia include metformin and TZDs while others reduce pp glucosew
- #31: thiazolidinediones increase insulin sensitivity by acting on adipose, muscle, and, to a lesser extent, liver to increase glucose utilization and decrease glucose production. One thiazolidinedione (pioglitazone) is currently available. The MOA is not fully understood CI; Heart failure or any evidence of fluid overload ●History of fracture or at high risk for fracture (eg, postmenopausal women with low bone mass) ●Active liver disease (liver transaminases >2.5 times above the upper reference limit), unless NASH is known to be the underlying cause of the elevation ●Active or history of bladder cancer ●Type 1 diabetes ●Pregnancy ●Macular edema
- #34: reabsorption of approximately 90 percent of the filtered glucose load SGLT2 inhibitors only lower plasma glucose levels by blocking reabsorption of filtered glucose, which falls as plasma levels fall. Thus, they do not usually cause hypoglycemia in the absence of therapies that otherwise cause hypoglycemia CI Type 1 diabetes ●Type 2 diabetes and eGFR <45 mL/min/1.73 m2 (ertugliflozin), or <30 mL/min/1.73 m2 (empagliflozin, canagliflozin, dapagliflozin, bexagliflozin) ●Prior diabetic ketoacidosis (DKA)
- #35: GLP1-RAs should not be combined with DPP4-i, as they both belong to the same class of incretins They should not be used in patients with a history of pancreatitis. • Should not be used in patients with a history of or a family history of MEN 2A or 2B or medullary thyroid cancer, gastroparesis
- #49: In severe hyperglycaemia, measured serum Na2+ is falsely low i.e. pseudohyponatremia. Recognition of pseudohyponatraemia is important to avoid use of hypertonic saline during fluid management. › Urea levels are not used for calculation of osmolality, as it passes freely across the plasma membranes and its accumulation does not induce an osmotic gradient across cell membranes