· Mayank Kashyap · 3 min read
Introduction to Diabetes Mellitus and it's classification
Excepts from Marrow faculty Rakesh Nair sir lecture and medicine book Harrison.
Classification
Pathophysiology
| Defect | Clinical/metabolic consequence | |
|---|---|---|
| 1 | ↓ Insulin secretion | Absolute/relative insulin deficiency → fasting & postprandial hyperglycaemia |
| 2 | ↑ Muscle IR | Impaired postprandial glucose disposal |
| 3 | ↑ Hepatic glucose output | Raised fasting glucose |
| 4 | ↑ Glucagon | Stimulates hepatic gluconeogenesis |
| 5 | ↓ Incretin effect | Less insulin after meals; inadequate glucagon suppression |
| 6 | ↑ Lipolysis | FFAs → IR, altered insulin secretion |
| 7 | ↑ Renal reabsorption | Higher renal threshold → hyperglycaemia maintained |
| 8 | CNS insulin resistance | Increased appetite, altered energy balance |
| 9 | Dysbiosis | Inflammation, metabolic endotoxemia |
| 10 | Inflammation | Adipose cytokines → IR & β‑cell stress |
| 11 | Impaired immunity | Worsened islet dysfunction & metabolic dysregulation |
| 12 | Genetics / epigenetics | Predisposition to T2DM; affects drug response |
| 13 | Sarcopenia | Lower glucose uptake capacity |
| 14 | Mitochondrial dysfunction | Reduced oxidative capacity → IR |
Diagnostic criteria
| Test | Diabetes (mg/dL) | Normal(mmol/L) | Pre Diabetes |
|---|---|---|---|
| Fasting plasma glucose (FPG) — after ≥8 hours fast | ≥ 126 mg/dL | <100 mg/dl | 100-125 mg/dl |
| 2‑hour plasma glucose during 75‑g OGTT | ≥ 200 mg/dL | <140 mg/dl | 140-199 mg/dl |
| HbA1c | ≥ 6.5 % | <5.7% | 5.7% - 6.4% |
| Random plasma glucose (with symptoms) | ≥ 200 mg/dL | <140 mg/dl | 140-199 mg/dl* |
*It’s not a official criteria.
Treatment
| Drug class | Primary mechanism of action | Representative agents (oral) | Key adverse effects / notes |
|---|---|---|---|
| Biguanides | ↓ Hepatic gluconeogenesis; ↑ insulin sensitivity; activates AMPK; modest ↑ peripheral glucose uptake. | Metformin | GI upset, lactic acidosis (rare; risk ↑ with renal impairment), B12 deficiency with long‑term use. Weight neutral or modest loss. |
| Sulfonylureas (secretagogues) | Close pancreatic β‑cell KATP channels → membrane depolarization → Ca2+ influx → ↑ insulin secretion (glucose‑independent). | Glimepiride, Glipizide, Glyburide (glibenclamide) | Hypoglycaemia risk (especially long‑acting agents), weight gain. Use cautiously in elderly and renal impairment. |
| Meglitinides (rapid secretagogues) | Similar to sulfonylureas (KATP channel modulators) but short‑acting—stimulate insulin release around meals. | Repaglinide, Nateglinide | Postprandial glucose control; hypoglycaemia risk less than sulfonylureas if meals skipped; weight gain possible. |
| Thiazolidinediones (TZDs) | PPAR‑γ agonists → ↑ insulin sensitivity in adipose tissue, muscle and liver; modify adipocyte differentiation and reduce lipotoxicity. | Pioglitazone, Rosiglitazone (less used) | Weight gain, fluid retention → heart failure risk, bone fractures; benefit: durable HbA1c effect and insulin sensitivity improvement. |
| Sodium‑glucose cotransporter 2 (SGLT2) inhibitors | Inhibit SGLT2 in proximal renal tubule → reduced renal glucose reabsorption → glycosuria → lower plasma glucose. | Canagliflozin, Dapagliflozin, Empagliflozin | Genitourinary infections, volume depletion, euglycaemic DKA (rare), ↓ CV & renal outcomes in selected patients (class benefit). |
| DPP‑4 inhibitors (gliptins) | Inhibit dipeptidyl peptidase‑4 → ↑ endogenous GLP‑1 and GIP levels → glucose‑dependent ↑ insulin secretion and ↓ glucagon. | Sitagliptin, Saxagliptin, Linagliptin, Vildagliptin | Well tolerated, low hypoglycaemia risk, modest HbA1c lowering. Saxagliptin linked to ↑ heart failure risk in some trials. |
| Alpha‑glucosidase inhibitors | Inhibit intestinal α‑glucosidases → delay carbohydrate digestion/absorption → reduce postprandial glucose rise. | Acarbose, Miglitol | Flatulence, diarrhea, abdominal pain; no hypoglycaemia alone (if hypoglycaemia occurs, must treat with glucose, not sucrose). |
| Oral GLP‑1 receptor agonist | GLP‑1 receptor agonism → glucose‑dependent insulin secretion, reduced glucagon, delayed gastric emptying, appetite suppression. | Oral semaglutide (Rybelsus) | GI side effects (nausea, vomiting), weight loss; injectable GLP‑1 RAs are more common; incretin‑based weight and CV benefits in some agents. |
| Bile acid sequestrant (glucose‑lowering effect) | Unknown exact mechanism (possibly altered FXR signaling, incretin effects); modest HbA1c reduction. | Colesevelam | Constipation, interference with absorption of other drugs; modest efficacy. |
| Dopamine agonist | Acts centrally to improve metabolic regulation (exact mechanism unclear); modest glucose‑lowering effect. | Bromocriptine QR | Rarely used; adverse effects include orthostatic hypotension, nausea; modest efficacy. |
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