​Kembara Xta - Medicine - Diabetes Mellitus Type 2

​Kembara Xta - Medicine - Diabetes Mellitus Type 2
Introduction 
In the presence of insulin resistance, diabetes mellitus (DM) type 2 is brought on by a gradual deficiency in insulin secretion.
Aspects of Geriatrics
Less aggressive glucose targets than in younger patients; monitor for hypoglycemia; alter doses for renal/hepatic failure and cognitive function Child Safety Considerations
The prevalence is rising and is similar to the obesity pandemic.
pregnant women's issues
Diet, insulin, metformin, and glyburide are all possible treatments for gestational diabetes.
Screening for diabetes and pre-diabetes in women with gestational diabetes should include an oral glucose tolerance test (OGTT) 6–12 weeks after delivery and every three years.


Prevalence and incidence of disease 
Incidence
Each year, there are 1.5 million new cases in the United States.
Prevalence
9.4% of Americans, or 30.3 million people, are estimated to have diabetes; 90–95% are presumably type 2.

Pathophysiology and Etiology 
Increased hepatic gluconeogenesis and peripheral insulin resistance with abnormal insulin secretion 
Genetic factors: typically polygenic; infrequently monogenic (e.g., mutations in the peroxisome proliferator-activated receptor [PPAR] and insulin genes); obesity (body mass index [BMI] 25 kg/m2; visceral adiposity); changes in the gut microbiome; drug- or chemical-induced (e.g., glucocorticoids, antiretroviral therapy, atypical antipsychotics, immunosup 

Genetics: Family history is a very reliable predictor of risk; common polymorphisms have a little causal influence; monozygotic twins have a 50% concordance rate.

Risk factors include: PCOS; gestational diabetes; gestational hypertriglyceridemia; low high-density lipoprotein (HDL); ethnicity: African American, Latino, Native American, Asian, and Pacific Islander; sedentary lifestyle; visceral obesity; and parental history of type 2 diabetes.

Prevention 
Reduce carbohydrate and overall calorie intake while maintaining a healthy weight; engage in moderate-intensity exercise for 150 minutes per week. 
Prediabetic patients taking metformin, -glucosidase inhibitors, thiazolidinediones (TZDs), and glucagon-like peptide-1 receptor agonist (GLP-1 RA).

Accompanying Conditions 
Hemochromatosis, acanthosis nigricans, PCOS, fatty liver disease, metabolic syndrome, hypertension, dyslipidemia, and dyslipidemia

History 
polydipsia, polyphagia, polyuria, weariness, blurred eyesight, neuropathy, and repeated infections are among symptoms. Many people do not exhibit any symptoms.

clinical assessment 

BMI, waist circumference, oral examination, cardiac examination, abdominal examination for hepatomegaly, focused neurologic examination, and examination of the feet for diabetics

Differential Diagnosis: Type 1 Diabetes Mellitus (DM) is one of the hallmarks of Cushing syndrome, acromegaly, and glucagonoma. Other features include low or nonexistent insulin, C-peptide, positive T-cell autoantibodies, and ketosis.


Laboratory Results 

Initial examinations (lab, imaging)
Criteria for diagnosis ● HbA1c ≥6.5% or ● Hyperglycemic symptoms and random plasma glucose ≥200 mg/dL (11.1 mmol/L) or ● Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) or ● 2- hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during OGTT with 75-g glucose load ● If equivocal, perform different test on same sample or a repeat test in a separate sample.

Management 
Although the effects on macrovascular outcomes are less obvious, strict glucose management prevents long-term microvascular problems. Those who have recently been diagnosed with DM, don't have any pre-existing DM issues, and have a long life expectancy will likely benefit from a more aggressive target.
Use a patient-centered approach. Modify your diet. Exercise frequently. Control your cardiovascular (CV) risk factors, such as your blood pressure and lipid levels. 
HbA1c targets: ADA and ACP standards have different goals.
- Long life expectancy, no cardiovascular disease (CVD), short course of diabetes, and no history of hypoglycemia; A1c 7.0 - A1c 8.0%: reduced life expectancy, advanced micro- or macrovascular problems, significant comorbidities, history of severe hypoglycemia or long-term DM when lower target is challenging to achieve – Most patients should have a HbA1c between 7% and 8%, according to the ACP (2).
Preprandial glucose levels of 80 to 130 mg/dL and postprandial levels of 180 mg/dL are advised by the ADA.

 Combine medications from various classes for complementing effects. If there are no contraindications, begin metformin monotherapy; if A1c is 9%, begin dual therapy; if BG is 300 mg/dL and the patient is symptomatic, consider adding insulin with or without GLP-1 analog.
Always take the side effect profile, cardiovascular benefit, renal benefit, and cost into account.

Steps in general Nephropathy: annual urine microalbumin-to-creatinine ratio and plasma creatinine (eGFR) Diabetic foot examination at every visit
 
Retinopathy: yearly diabetic eye exam; moderate- to high-intensity statins if 40 to 75 years old.
If you are over 50, take low-dose aspirin if you have one more CV risk factor and have a low risk of GI bleeding.
 Hypertension: target BP 140/80 mm Hg
  The annual influenza vaccine, the pneumococcal (PPSV23) vaccine for adults, and the pneumococcal conjugate vaccine (PCV13) for patients over 65 (and some younger; consult the CDC).

First Line of Medicine

Metformin is preferred due to its excellent effectiveness in decreasing blood sugar, strong safety profile, reduced risk of hypoglycemia, inexpensive cost, and ability to cause weight loss. 
Some studies indicate a benefit for the cardiovascular system; dosage: 500 to 2,000 mg in divided doses BID or extended release QD
Avoid owing to risk of lactic acidosis in cases of severe acute illnesses such liver disease, cardiogenic shock, pancreatitis, and hypoxia. Caution in cases of acute heart failure, alcohol misuse, and in the elderly; linked to vitamin B12 deficiency.
 Reduce the dose to 1,000 mg in CKD for eGFRs between 30 and 45; discontinue if eGFR 30.
In 10% of patients, severe diarrhea necessitates switching to a different medication. 

Third and Fourth Line

 Fundamental concepts
- Add a second or third agent if your HbA1c is above target.
Consider using medications that help patients with CAD, heart failure, or CKD if they have these conditions.
Consider drug-specific adverse effects including hypoglycemia and weight gain. The cost of the medication is a crucial factor.
- Consult with patients to improve adherence.
(Incretins) GLP-1 RA
- Improve insulin release that is glucose-dependent.
- Encourage weight loss; no danger of hypoglycemia; some enhance cardiovascular results.
Acute pancreatitis is a remote possibility. Use with caution in stage 4 of CKD. may make gastroparesis worse. Most are pricey injectables.
- Contraindicated in those with a personal or family history of medullary thyroid carcinoma or type 2 MEN
- Exenatide (5–10 mg SC BID; Byetta) or exenatide ER (Bydureon) 2% per week - Improved CV outcomes with liraglutide (Victoza): 0.6 to 1.8 mg/day (3) - Improved CV outcomes with dulaglutide (Trulicity): 0.75 to 4.50 mg weekly (3) 20 g SC QD of lixisenatide (Adlyxin).
- Semaglutide oral (Rybelsus) 3 to 14 mg daily neutral CV risk; injectable (Ozempic) 0.25 to 1.00 mg weekly improved CV outcomes (3) 
Weight reduction occurs as a result of SGLT2 inhibitors, which also pose no risk of hypoglycemia.
- The use of canagliflozin, dapagliflozin, and empagliflozin decreased admissions for heart failure and slowed the progression of renal disease.
The CV mortality rate was improved with empagliflozin and canagliflozin.
-Canagliflozin prevented death from renal causes in patients with albuminuria and GFRs between 30 and 90.
- In individuals with a GFR of 25 to 75, dapagliflozin delayed the course of renal disease and decreased mortality due to renal or CV causes (6).
- An increase in UTI and vaginal mycotic infections. risk of euglycemic diabetic ketoacidosis (DKA) increased; relatively high cost - If eGFR is 45 or higher, do not start therapy.
- Invokana (canagliflozin): 100 to 300 mg/day
- 5 to 10 mg per day of dapagliflozin (Farxiga).
- Jardiance (empagliflozin): 10 to 25 mg daily
Dipeptidyl peptidase-4 (DPP-4) inhibitors - Inhibit DPP-4 enzyme, which deactivates endogenous GLP-1 and GIP. - Ertugliflozin (Steglatro): 5 to 15 mg daily
Low risk for hypoglycemia; dose reduction necessary for all drugs except linagliptin in renal impairment.
No indication of a reduction in CV risk due to weight (7).
- Saxagliptin (Onglyza): 2.5 or 5.0 mg per day - Sitagliptin (Januvia): 100 mg per day
Sulfonylureas: Linagliptin (Tradjenta): 5 mg/day; Alogliptin (Nesina): 25 mg/day; Caution with renal or hepatic illness, sulfa allergy, creatinine clearance 50 mL/min; May induce weight gain, hypoglycemia
- Cost-effective
- Glipizide (Glucotrol): 2.5 to 40.0 mg/day; Glipizide extended-release: 5 to 20 mg/day; - Glyburide (DiaBeta, Micronase): 1.25-20.00 mg/day; - Glynase: 0.75 to 12.00 mg/day; - Glimepiride (Amaryl): 1 to 8 mg/day TZD; - Pioglitazone - May make heart failure symptoms worse
Pioglitazone (Actos): 15 to 45 mg/day; Rosiglitazone (Avandia): 4 to 8 mg/day; Insulin: - Increases glucose elimination, decreases hepatic glucose synthesis - Powerful glucose reduction; safe
- In patients with A1c > 10%, catabolic symptoms, and ketosis, consider this as initial therapy.
- After attempting dual or triple therapy, use as supplemental therapy.
- Weight gain; increased risk of hypoglycemia
- Although more expensive than NPH and ordinary insulin, analogs have a lower risk of hypoglycemia.
- No negative impact on CV results
- The starting dose of basal insulin is 0.1–0.3 U/kg/day. Tirate up for the desired outcome. If postmeal glucose levels are high, increase mealtime (rapid/short-acting) insulin. Starting doses for meals might be 4 U or 10% of the baseline dosage.
- Lispro (Humalog), aspart (Novolog), and glulisine (Apidra) are rapid-acting analogs with an action time of 3 to 5 hours; Fiasp and lispro-aabc are ultrarapid analogs. faster start - Afrezza, an inhaled form of insulin, acts quickly and lasts for 4.5 hours. - Human regular short-acting insulin (Humulin R/Novolin R/ReliOn R) has an action time of 6 to 8 hours. – Human NPH (Humulin N/Novolin N/ReliOn N) has a half-life of 13 to 20 hours, while human regular U-500 (Humulin R U- 500) has a half-life of 6 to 10 hours. – Premixed insulin products include NPH/regular 70/30 (Novolin 70/30, Humulin 70/30), 70/30 and 50/50 aspart mix (Novolog mix), and 75/25 and 50/50 lispro mix (Humalog mix). Basal insulin analogs include glargine U-100 (Lantus, Basaglar) for 22 to 24 hours, glargine U-300 (Toujeo) for 36
 Amylinomimetic: Reduces prandial insulin by 50%; delays stomach emptying; blunts glucagon; increases satiety.
Pramlintide (Symlin): 60 to 120 g SC before meals; Glucosidase inhibitors; slows intestinal carbohydrate digestion; avoid in cases of renal insufficiency and bowel disorders.
- Reduces post-meal hyperglycemia
25 to 100 mg TID of acarbose (Precose).
- Miglitol (Glyset): TID doses of 25 to 100 mg
Meglitinides: Taken at the start of meals, they have a mechanism similar to SU but a significantly shorter duration of action.
- 0.5 to 4.0 mg TID of repaglinide (Prandin).
60 to 120 mg TID of nateglinide (Starlix).
Combination therapy combines drugs from various classes with complementary modes of action.


Surgical Techniques 
Consider bariatric surgery for patients with a BMI of 35 kg/m2 or higher.
education on diabetes self-management


Prognosis 

an average lifespan under proper care

Complications and Emergencies include foot ulcers, Charcot joints, hyperosmolar coma, DKA, ASCVD, peripheral vascular disease, and stroke. 
Microvascular: retinopathy, diabetic CKD, and neuropathy
GI: fatty liver illness, gastroparesis; ophthalmic: blindness, cataracts, glaucoma