Diabetes Type 2

Definition Formerly non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes – is a metabolic disorder that is characterized by highblood glucose in the context of insulin resistance and relative insulin deficiency.

Epidemiology 5% of Irish population have Type 2 diabetes Common in Western countries/lifestyles- the diet contains more calories with less caloric expenditure. If diagnosed before age 40, average reduction in life-years is 12 years (male) and 19 years (female) Lifetime risk of developing diabetes if born in 2000 is 33% (male) and 39% (female)

Risk Factors Family history: 1st-degree relative Gestational diabetes (GDM) Obesity: Induces resistance to insulin-mediated peripheral glucose uptake Ethnicity: African American, Latino, Native American, Asian American, and Pacific Islander Impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) Genetics Strong polygenic familial susceptibility Concordance nearly complete in identical twins

Pathophysiology Progressive defects in insulin secretion and peripheral insulin action (“insulin resistance”)

Aetiology Genetic factors (B-cell dysfunction, defects in insulin action, diseases of the exocrine pancreas, i.e., cystic fibrosis) Obesity, immune-mediated, infection, hemochromatosis Drug- or chemical-induced (e.g., medications used for psychosis, HIV, or transplant recipients) Commonly Associated Conditions Hypertension Hyperlipidemia Impotence Infertility Syndrome X/metabolic syndrome Renal insufficiency/failure Cardiovascular disease Retinopathy Stroke Pancreatic cancer Polycystic ovary syndrome Acanthosis nigricans

Investigation

Criteria for testing	In all individuals who are 45 years and above: particularly in those with a BMI > 25kg/m2 and if normal should be repeated at 3-year intervals Testing should be considered at a younger age or carried out more frequently in individuals who are overweight (BMI > 25kg/m2*) and have additional risk factors:
History	Polyuria, polydipsia, polyphagia, weight loss, weakness, fatigue, and frequent infections
HbA1C	has advantages over plasma glucose analyis. If testing is not possible, previously recommended diagnostic methods are acceptable
Glucose tolerance test (GTT)	The test should be done in the morning after an overnight fast of between 8 and 14 hours and after at least 3 days of unrestricted diet (> 150g carbohydrate per day) and unlimited physical activity. The person should remain seated and should not smoke throughout the test. Blood should be drawn at T0 and 2 hours.
Fasting Plasma Glucoe (FPG)	Fasting is defined as no caloric intake for at least 8 hours.
Criteria for diagnosis	At least one from below HbA1C > 6.5%. Diagnosis should be confirmed with a repeat test Symptoms of diabetes plus random plasma glucose ≥200 mg/dL (11.1 mmol/L) FPG ≥126 mg/dL (7.0 mmol/L) on 2 occasions 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during oral GTT with 75-g glucose load
2006 WHO Diabetes criteria	Condition 2 hour glucose Fasting glucose mmol/l(mg/dl) mmol/l(mg/dl) Normal <7.8 (<140) <6.1 (<110) Impaired fasting glycaemia <7.8 (<140) ≥ 6.1(≥110) & <7.0(<126) Impaired glucose tolerance ≥7.8 (≥140) <7.0 (<126) Diabetes mellitus ≥11.1 (≥200) ≥7.0 (≥126)
Diagnosis of GDM	*

Management
HSE: A Practical Guide to Integrated Type 2 Diabetes Care (Updated 2008)

Initial assessment	Blood Pressure Weight/Height (Calculate BMI), waist circumference Family History/Drug history and current medication Medical History Complications Lifestyle, including smoking status, physical activity, diet Foot status, eye review
Investigations:	HbA1c Fasting Lipid profile Full blood count Microalbuminuria Serum creatinine Serum Iron Serum Transferrin Thyroid Function Tests 12-lead ECG
Medication	Metformin (Biguanides): Preferred 1st medication due to its effects on weight loss and insulin resistance. Metformin (Glucophage, Fortamet, Riomet, Glumetza): 500–1000 mg b.i.d.–t.i.d. or long-acting per day. Max 2550 mg/d, except Glumetza 2000 mg/d Avoid situations that increase risk for lactic acidosis: Renal insufficiency, radiocontrast agents, surgery, or acute illnesses, i.e., liver disease, cardiogenic shock, pancreatitis, or hypoxia Caution with congestive heart failure (CHF), alcohol abuse, elderly, or with tetracycline Precautions: Warn patients of signs of hypo- and hyperglycemia: Combination therapy of metformin and sulfonylurea can increase patient's relative risk of cardiovascular hospitalization or mortality Sulfonylureas Glipizide (Glucotrol): 2.5–40 mg/d; dosage >10 mg/d give b.i.d., taken 30 minutes before meals Glipizide extended-release: 5–20 mg/d Glyburide (DiaBeta, Glycron, Glynase, Micronase): Nonmicronized tablets 1.25–20 mg/d or micronized tablets 0.75–12 mg/d in 1–2 doses Glimepiride (Amaryl): 1–8 mg/d Caution with renal, liver, or thyroid disease, sulfa allergy, Cr CL <50, late pregnancy Thiazolidinediones (TZD): Pioglitazone (Actos): 15–45 mg/d Rosiglitazone (Avandia): 2–4 mg b.i.d. Monitor serum transaminase q.2mo. for the 1st year, contraindicated for liver disease and symptomatic heart failure patients. May cause or exacerbate CHF and myocardial infarction. Avandia: Increased risk of cardiovascular events Alpha-glucosidase inhibitors: Acarbose (Precose): 25–100 mg t.i.d. Miglitol (Glyset): 25–100 mg t.i.d. Taken at beginning of meals to decrease postprandial glucose peaks Poor patient compliance due to gastrointestinal symptoms Avoid use in renal insufficiency, inflammatory bowel disease, colonic ulceration, or partial bowel obstruction Dipeptidyl peptidase-4 (DPP-4) inhibitor: Sitagliptin (Januvia): 25–100 mg/d, starting dose 100 mg/d Vildagliptin (Galvus) awaiting Food and Drug Administration (FDA) approval Can use alone or in combination with TZD, metformin, or sulfonylureas Renally excreted; therefore, adjust dosage for renal patients Insulin Rapid (Aspart, Lispro, Glulisine), short (regular insulin), intermediate (NPH), and long/peakless (Glargine) or long/peak (Levemir): Can be given up to t.i.d May be used in combination with oral agents, or with an insulin of a different half-life Most often required in late stages of type 2 DM when oral agents fail to control glucose le Insulin detemir (Levemir): 0.77 U/kg, onset 1 hour, no true peak, duration 6–23 hours, given daily or b.i.d.
Other/second lines treatment	Pramlintide (Symlin):Amylinomimetic: Synthetic analog of human neuroendocrine hormone amylin Exenatide (Byetta):Synthetic analogue of exendin, a GLP-1 agonist, found in Gila monster saliva Meglitinides: Repaglinide (Prandin) or Nateglinide (Starlix)
Glycaemic control	Composite criteria by the major organisations (IDF, EASD, ADA, Diabetes UK) recommend: Target HbA1c for Type 2 diabetes should be set under 6.5%, which equates to fasting glucometer levels at home mainly in the 5s and 6s. A target Pre-prandial capillary glucose of less than 6.0mmol/l. Peak post-prandial capillary glucose should if possible be less than 8.0mmol/l.
Pt self control	Patients on insulin should strive to record their home blood glucose readings using a glucometer four times a day (before each meal and at bedtime). Patients with satisfactory HbA1c levels should test at least once daily between fasting levels and 1 hour post-prandial levels. The quality control of the monitor should be checked four times a year at a minimum. Monitors should be changed / upgraded every two years. Patients should be advised to record home glucose readings in their patient record book, and to bring their book to each of their diabetic reviews.
Ongoing care	At least every 3 months- new symptoms, results, diet, physical activities, psycososial, foot risk factor, obese pt see dietician on a monthly basis Community Orientated Diabetes Education (CODE) Exercise : Aerobic exercise is beneficial in diabetes with the greater the amount of exercise the better the results.It leads to a decrease in HbA1C, improved insulin resistance, and a better V02 max
Annual review	Symptoms of IHD, PVD, neuropathy, Erectile Dysfunction Feet- footwear, joint deformity Eyes, kidneys, arterial risk, podiatry, dietician
In pregnancy	Women contemplating pregnancy need to be seen frequently by MDT At 45 to 60 days postnatally, women with gestational diabetes should be reviewed and screened with a 75gm glucose tolerance, if non-diabetic, they should be advised about healthy lifestyles, their risk about developing future diabetes, need to plan future pregnancies and exclude diabetes before future pregnancies, and should be screened with a glucose tolerance test every 1-2 years
Emergencies	Hypoglycaemia Hypoglycaemia can occur in any patient using insulin or sulphonylureas: When treating early hypoglycaemic attack use 1 glass of glucose drink or sugar containing mineral or 85-100mls of Lucozade or 4-6 glucose tablets. Follow this with a longer acting snack e.g. slice of bread if meal is not due within a half an hour. A severe hypo may require double carbohydrate intake  i.e. 30gms. Hypoglycaemia unawareness Repeated hypoglycaemia can induce hypoglycaemia unawareness. Consider (by self-testing) the possibility of undetected night-time or other hypoglycaemia Nocturnal hypoglycaemia Consider : taking a bed-time snack using shorter-acting sulphonylureas or repaglinide ensure that insulin dose and regime are appropriate Hypoglycaemic coma / fitting Two doses of 50 mls of 20 % glucose IV  if unconscious, or 2 doses of 1 mg glucagon IM. Beware of poor glucagon effect in the starved or inebriated patient. Follow with oral carbohydrate and review for possible relapse. Train carers to use glucagon if hypoglycaemia is a recurrent problem and ensure supplies remain in date.

Complications

Microvascular

Retinopathy Eg: Blindness, Glaucoma, Cataracts Management All patients should have an initial dilated and comprehensive eye examination by an ophthalmologist shortly after diagnosis. Subsequent examinations should be repeated annually. On fundoscopy:cotton wool spots, flame hemorrhages and dot-blot hemorrhages. Nephropathy Eg: Chronic renal failure Management Serum creatinine and urine albumin/creatinine ratio (ACR) should be measured at diagnosis and annually thereafter. The urine ACR should be measured on an early morning specimen. Two out of three urine ACR results need to be positive over a 6 month period to indicate nephropathy. Neuropathy Eg: Skin ulceration, charcot joint Management Detect neuropathy with a 10g monofilament. See Peripheral Arterial Disease under Macrovascular complications. Reconstructive surgery for charcot joint

Macrovascular

Cerebrovascular disease Eg: Hyperlipidemia, hypertension Management A full clinical history including history of CVD should be taken at initial diagnosis and once a year. The 10-year risk of CVD should be estimated annually for all patients without overt CVD using risk assessment charts. Blood pressure control is as important as blood glucose control. Target SBP <130mm/Hg    DBP < 80mm/H LDL goal of <70 mg/dL in patients with existing CVD Peripheral arterial disease Eg: diabetic foot, gangrene of extremities Management Assess arterial circulation by measuring dorsalis pedis and posterior tibial foot pulses; measure Doppler ankle : brachial pressure ratio if available. Check for callus formation The provision of orthoses or therapeutic shoes or both can reduce abnormal foot pressure, callus formation and therefore ulcer development.

Prognosis In susceptible individuals, complications begin to appear 10–15 years after onset, but can be present at time of diagnosis since disease may go undetected for years. Life expectancy may be reduced by five to ten years, mainly because of premature cardiovascular disease The risk of myocardial infarction and stroke is two to five times higher than in the general population Pre-menopausal women lose their protection against macrovascular disease It is the most common cause of non-traumatic lower limb amputation It is the most common cause of blindness in adults of working age. It is the single most common cause of end-stage renal disease About 30% of patients will develop overt kidney disease Impotence may affect up to 50% of men with longstanding diabetes