Novel strategies for Glycemic Control and preventing diabetic complications

1. Novel strategies for glycemic control and preventing diabetic complication applying the clustering based classification of adult onset DM Professor / Mohammed Ahmed Bamashmos ( MD) Professor of Internal Medicine and Endocrinology Faculty of Medicine , Sanaa University

2. Introduction Is the current treatment of DM depends on an evidence based medicine The current treatment depends only on ; - the presence or absence of ASCVD , HF , CRD - any risk factors of ASCVD , HF - Risk of hypoglycemia - presence of obesity - patients preference - cost It fail to address on the etiology and pathogenesis ( evidence based medicine ) The novel treatment ; - concentrate on the etiology and pathogenesis which is important for ; - prevention strategies

3. - choosing proper treatment - expecting and preventing long term complication depending on the etiology and pathogenesis In order to achieve these goals any newly diagnosed DM should be subjected to the following ; 1- clinical assessment ; - Age - Body weight 2- Laboratory assessment ; - HbA1C - Presence of autoantibodies ( GAD ) - Presence of IR ( HOMA-IR ) - Assessment of beta cell function ( serum c- peptide )

4. According to this assessment any newly diagnosed DM is sub classified into 5 subgroups ;

5. steps of the novel treatments 1- Estimate the pathophysiology ; based on the clinical and laboratory assessment - Age ; with increased age there is - increased prevalence of type 2 DM ( MARD , 39% ) - increased prevalence of obesity particularly central - IR as age is risk factors of IR • Body weight ; Assessment of obesity ; - By BMI - if BMI is less than than 25 use WC

8. Rule of obesity in the pathogenesis of type 2 DM and its complication

9. - severity of hyperglycemia ; Rule of hyperglycemia in the pathogenesis of diabetes related complication

10. - presence of autoantibodies ; - for DD of different subgroups - for staging and prevention of type 1 DM - Choosing proper treatment • Presence of IR ; - Staging and progression of type 2DM - Prevention strategies of type 2 - choosing proper treatment - to expect long term complication linked to IR

11. Pathogenesis of IR related complication ; - hyperglycemia - obesity - hypertension - microalbuminuria - hyperuricemia - endothelial dysfunction - inflammation , oxidative stress - dyslipidemia - beta cell dysfunction

12. - Rule of beta cell dysfunction ; - staging of type 1,2 DM - sub classification of newly diagnosed - Choosing proper treatment ;

14. 2- Determine optimal AIC target

15. 3- Set optimal body weight target ; Treatment target ; Weight loss of 5–10% of baseline body weight is recommended as an initial goal of treatment, Treatment indication ; - the AACE and ACE guideline recommended that patients with DM and BMI ≥ 27 kg/m - WC is more than 102 cm in male or 88 cm in female treatment types - Diet and exercise - Drugs - oral antidiabetic drugs ;

16. Other drugs ;

17. Benefit

18. 4- Do diet and exercise to active optimal A1C and body weight target 5- choice drugs According to the etiology and pathogenesis - drugs that decrease body weight in patients with MUO - Drugs that has good glycemic efficacy

20. - has no hypoglycemic effect

21. - Hyperglycemic issue ( glycemic variability ) There are three main components of dysglycemia in DM patients: chronic hyperglycemia, hypoglycemia, and glycemic variability (GV). The clinical term GV biologically refers to the blood glucose oscillations that occur throughout the day (short-term GV), including hypoglycemic periods and postprandial glucose increases, as well as the blood glucose oscillations that occur at the same time on different days (long-term GV).

23. Treatment according to different subtype

24. Preventing diabetic complications complication according to different subtype

25. A- SAID ; Science the main pathogenesis is immune mediated destruction of baet cell , so its characterized by ; - positive autoantibodies - severe hyperglycemia - very low c- peptide So main complication is related to hyperglycemia as neuropathy and retinopathy , obesity and dyslipidemia and CV complication are less frequient than type 2DM Treatment - insulin to achieve tight glycemic control B- SIDD ; Its characterized by

26. - non immune mediated beta cell destruction - negative autoantibodies - severe hyperglycemia - very low c- peptide So main complication is related to hyperglycemia as neuropathy and retinopathy , obesity and dyslipidemia and CV complication are less frequient than type 2DM Treatment ; - goal ; tight glycemic - types ; - oral ; - insulin secretogoues - DPPT4I - Insulin or GLP1RA

27. 3- SIRD ; Since the main pathogenic mechanism is obesity , IR , so the expected complication is related to this; - dyslipidemia - hypertension - CAD , HF - MAU, CKD Treatment - use drugs that prevent these complication ( primery prevention ) by choosing drugs that ; - has proper glycemic control - decrease body weight - improve insulin sensitivity

28. drugs ; - SGLT2I - Metformin - GLP1RA - DPPT4I - Tirzepatide if the patients already has ASCAVD , HF , CRD or any risk factors Use drugs same as current treatment algorithm

29. 4- MOD ; - mild obesity ; MHO - mild to moderate IR - mild to moderate beta cell dysfunction Complication ; - low prevalence of diabetic retinopathy and neuropathy - low prevalence of CHD , HF - senile complications including frailty, fracture, and cognitive impairment are frequent Treatment - life style  

30. - Drugs - Metformin -SGLT2I - DPPT4I - If the insulin secretory capacity is decreased because of long duration of DM we can use insulin secretagogues

31. 5- - MARD ; Aging can promote onset of ASCVD, heart failure and AF in MARD. Elderly patients with MARD are vulnerable to hypoglycaemic events such as cognitive impairment and fall-related fractures. To prevent hypoglycaemic episodes, the use of insulin and insulin secretagogues should be minimised. A recent meta-analysis of patients with T2DM indicated that DPP-4 inhibitor use had the lowest risk and insulin use had the highest risk of dementia [95]. The side effects of antidiabetic drugs on skeletal integrity are vitally important in elderly patients because they are linked to fall-related fracture