| What is DM? | Condition where there is chronic raised blood glucose concentration, caused by absolute or relative lack of insulin, either not being produced or insufficient production or insufficient action on body. |
| What are symptoms of DM? | Many are asymptomatic, symptoms include (polyuria, polydipsia (thirst), polyphagia (appetite), unexplained weight loss, recurrent blurred vision, generalized pruritis/ vulvovaginitis, peripheral neuropathy, sexual dysfunction, recurrent skin infections |
| What is type 2 DM? | Characterized by chronic hyperglycemia, associated w/micro and macrovascular complications, generally arises from insulin resistance and b-cell dysfunction (both).
Non-insulin dependent DM (not insulin dependent for life, age 30+ at dx, usually obese, few classic symptoms, ketoacidosis is rare)
Usually at beginning we have insulin resistance and deficit of insulin, then we get combination of impaired insulin secretion and insulin resistance. |
| What is type 1 DM? | Due to destruction of beta cells of islets of pancreas, leads to absolute deficit in insulin, A subtype is autoimmune, and B subtype is idiopathic. |
| What are other specific types of DM? | Due to genetic defects of beta cells (in insulin function), due to disease influencing exocrine functions (secondary to endocrine damage), due to endocrinopathies, drugs, chemicals, infections, metabolic and genetic disturbance. |
| What is gestational DM? | Glucose intolerance onset for first time during pregnancy |
| How is dx of GDM? | Two step approach, women 24-48 weeks of gestation perform first 1-hour plasma glucose after 50-g oral glucose load (if level is >130/135/140) perform a 100-g OGTT
If 2 of 4 are seen we make dx (fasting >95mg/dl, 1hour >180mg/dl, 2hour >155 mg/dl, 3hour >140mg/dl)
Another approach is one step approach, 75-g OGTT see glucose at fasting, after 1 hour and after 2 hours if any of 3 criteria occurs it is dx (fasting>92mg/dl, 1hour>180mg/dl, 2hour>153mg/dl) |
| What are monogenic forms of DM? | Cause beta cell dysfunction (neonatal DM and MODY) small fraction of pt w/ DM (<5%), under 6 months of age, 80-85% of cases monogenic cause.
Most common cause is maturity-onset diabetes of the young (MODY), which is hyperglycemia onset in early age (<25 years), characterized by impaired insulin secretionw/ minimal or no defects in insulin action, auto dominant in 13 genes. |
| What is main difference between old and new classification ofDM? | New (no IDDM and NIDDM, no DM due to malnutrition, no primary and secondary)
Terms used are IFG and IGT |
| What are diagnostic criteria of DM? | symptoms + RPG >200 mg/dl, FPG >125 mg/dl (fast at least 8 hours), 75g-OGTT >200mg/dl.
IFG>100 and <126mg/dl
Modernization is thought to increase T2DM (due to lack of exercise and fatty diet) |
| How is metabolic staging of DM? | Obesity causes insulin resistance, causing hyperinsulinemia, leads to IGT, coupled w/beta cell defect causes decreased insulin secretion leading to early diabetes, and w/beta cell failure we get into late diabetes. |
| How is normal physiology of regulation of hyperglycemia? | insulin secretion, carb absorption in gut, glucose uptake in muscles w/insulin resistance, decreased glucagon, incretin (GLP-1) effect, NT effect, kidney glucose reaborption decrease, hepatic glucose uptake and fat glucose uptake all play a role in decreasing hyperglycemia. |
| How is pathophysiology of T2DM? | Genes cause impaired insulin/ resistance lead to IGT and thus T2DM.
We may see increased glucagon and decreased insulin be pancreas (apoptosis, lipotoxicity, amyloidosis), increased hepatic glucose output, muscle insulin resistance and decreased glucose uptake leading to hyperglycemia, decreased incretin effect, increased renal reabsorption (SGLT2 upregulation due to hepatocyte nuclear factor-1 alpha stimulation), lipolysis all can lead to hyperglycemia (Omnious Octet)
we see inflammation of islets and decrease in beta cell mass and secretion, inflammation is caused by dyslipidemia, hyperglycemia and circulating adipokines. |
| How is the continuum of CV risk in T2DM? | Genetics + Environemental factors (obesity/physical inactivity) create insulin resistance and thus IGT (this leads to hyperinsulinemia, increased TG decreased HDL, atherosclerosis, and HTN), then we get diabetes onset we see more atherosclerosis, hyperglycemia and HTN, more ongoing DM lead to retinopathy, nephropathy and neuropathy, finally lead to blindness, renal failure, CHD, amputation and optimally death |
| What is insulin resistance? | Major defect in T2DM, reduced biological response to insulin, strong predictor of T2DM and closely related to obesity (more than 80% of pt w/ T2DM have insulin resistance, it leads to increased liver glucose output, decreased muscle glucose uptake, decreased adipose glucose uptake causing hyperglycemia
It doubles risk of CVD, half of pt w/CHD and T2DM have insulin resistance
It leads to hyperglycemia, dyslipidemia, HTN, vascular damage, clott, inflammation (as much of a risk of CVD as smoking) |
| What is beta cell dysfunction? | Major defect in individuals w/T2DM, reduced ability to secrete insulin in response to hyperglycemia.
Occurs due to chronic hyperglycemia, glucotoxicity, oversecretion of insulin in response to insulin resistance, lipotoxicity |
| What is the incretin effect? | After ingesting a meal, GI releases incretins (active GLP1 and GIP) leading to activation of insulin secretion and decrease in glucagon secretion
70% of individual insulin secretion after a meal is due to incretins.
GLP1 (from L cells of ileum and colon, stimulates insulin response, inhibits gastric emptying, glucagon, reduces food intake)
GIP (released from K cells of duodenum, similar effects, minimal gastric emptying effect
Gut, immune cells and Enteroendocrine cells are targets for control of inflammation of gut mucosa by GLP1 |
| What drugs act as antidiabetics on incretin effect? | GLP1 analogs (increase glucose dependent insulin secretion, resistant to DPP-IV degradation)
DPP-IV inhibitors (decrease GLP1 degradation and increase glucose dependent insulin secretion. |
| What are serious complications associated w/ DMT2? | Diabetic retinopathy, diabetic nephropathy, stroke, CVD, diabetic neuropathy. |
