Diabetes

1- Definition:

Diabetes criteria are:

– A fasting plasma glucose ≥ 1.26 g / L (or 7 mmol / L) or less 2 times

– A plasma glucose at any time of day ≥ 2 g / L (11.1 mmol / L)

– A blood glucose 2 hours after a glucose load (75g OGTT) ≥ 2 g / L (it is no longer appropriate to achieve the OGTT in diabetes diagnostic framework)

– The OGTT is useful to define two groups:

– Moderate fasting hyperglycemia: fasting plasma glucose> 1.10 g / L and <1.26 g / L. Plasma glucose (2 hours after a glucose load) <1.4 g / L

– Glucose intolerance: fasting glucose <1.26 g / L and ≥ 1.4 g / L two hours after a glucose load (but <2g / L).

– The diagnosis of impaired fasting glucose is a pending diagnosis and to recommend close monitoring (high risk of developing diabetes)

– Glucose intolerance appears to be a separate group without increased risk of diabetes

– The OGTT is no point in people over 70 years (the therapeutic approach does not depend on the results).

– The OGTT is not of interest to fasting hyperglycemia without diabetes between 1.1 and 1.26 g / L associated with insulin resistance metabolic syndrome components (obesity, hypertension …) …

2- Classification:

A- type 1 diabetes:

a- Linked to the autoimmune destruction of beta-cells Langerhans

b- Idiopathic

B- type 2 diabetes:

Combining insulin resistance and decreased endogenous insulin to varying degrees

C- Gestational Diabetes:

It is a state of intolerance to glucose, regardless of its severity, appeared during pregnancy in a woman without previously known diabetes mellitus.

D- Other types:

* Genetic Defect of ß-cell function: MODY

* Diabetes mitochondrial mutation of mitochondrial DNA

* Genetic defect of insulin action: insulin resistance type A diabetes lipoatrophic

* Pancreatic Diabetes: pancreatitis, pancreatic cancer, chronic pancreatitis, cystic fibrosis, hemochromatosis.

* Endocrine: acromegaly, Cushing’s syndrome, pheochromocytoma, hyperthyroidism, primary aldosteronism (Conn disease)

* Diabetes induced by drugs: corticosteroids, diazoxide, adrenergic agonists, thiazide diuretics, α-interferon …

* Infections: congenital measles, CMV …

* Rare forms associated with an autoimmune disease (anti-insulin receptor Ac)

* Other genetic diseases sometimes with diabetes: trisomy 21; Klinefelter syndrome; Turner syndrome; Friedrich ataxia; Huntington …

3- Special Diabetes:

A- Diabetes MODY:

– Represents nearly 5% non-insulin dependent diabetes

– Early onset Diabetes (25 years) with autosomal dominant with high penetrance; they are charac-SES by abnormalities in insulin secretion.

– Mutation of glucokinase gene or other

– The move towards insulinoréquérence may be more able slower

B- Mitochondrial Diabetes:

– Purely maternal transmission to diabetes due to mutations of mitochondrial DNA (1-10% of diabetes)

– Combines with bilateral sensorineural hearing loss, atypical retinitis pigmentosa, various neurological signs

– Muscle biopsy of the lesions found in mitochondrial myopathies.

– May occur at any age and often evolve towards insulinoréquérence (abnormal insulin secretion)

C- syndrome of severe insulin resistance:

– Generally associated with nigricans achanthosis and often accompanied by hyperandrogenism

– The anomaly may be located at the insulin receptor level; or the presence of insulin antibodies; anomaly or downstream of the insulin receptor

D- Gestational Diabetes:

– Defined as a disorder of glucose tolerance, diagnosed for the first time during pregnancy regardless of changes in the postpartum period.

– It concerns 1.5 to 6% of all pregnancies

– Screening (systematic for some or before FDR) is made between the 24th and 28th week of gestation by the test O’Sullivan

– Test O’Sullivan: is to measure plasma glucose one hour after the oral glucose load of 50 g, when glucose levels> 1.30 g / L must perform the OGTT (glucose 100g)

– The diagnostic criteria for DG are: very difficult, divergent, you have seen elsewhere (in my classes)

– Complications: there is no fetal malformation; the main risk is macrosomia

– In the long term the risk of type 2 diabetes in the mother is 20 to 50% of cases. For the child, risk and obesity on one hand and type 2 diabetes on the other (long-term)

4 Type 1 Diabetes:

– Genetic Plot: HLA DR3-DR4 and HLA DQ (not non-ASP-ASP) / but also environmental factors (virus)

– Auto-antibodies: anti-islets (ICA); anti-GAD (glutamate decarboxylase acid); anti-insulin; IA2.

– Children and young adults (<35 years). Cardinal signs (asthenia, polyuria, polydipsia, polyphagia contrasting with weight loss). Ketonuria

– The signs regress after 24 to 48 hours of insulin therapy.

– Ideally blood glucose should range between 0.70 and 1.40 g / L and glycosylated hemoglobin (HbA1c) remains below 7.0%.

– The insulin syringe or pen are titrated to 100 IU / ml

– Only rapid insulins are used intravenously; the intermediate-acting insulin and delay are for the subcutaneous route. The duration of action of insulin injected intravenously is approximately 60 minutes.

– Insulins should not be mixed at the time of injection

– The protamine zinc insulins should not be mixed with regular insulin.

– A single daily injection of long-acting insulin if life expectancy is limited or for social or psychological reasons (adolescent). Provided insulin requirements are low.

– Three (or four) are usually necessary especially in young patients

– The dosage cruising is between 0.7 and 0.9 U / kg / day. During adolescence the needs are greater (1 to 1.5 U / kg).

– Discovering diabetes in the absence of ketosis and obesity, it starts between 0.3 and 0.4 U / kg.

– Lipodystrophy: lipohypertrophy (too superficial injection or repeatedly at the same site); lipoatrophy (immunological, exceptional since the abandonment of animal insulins).

– Capillary blood glucose before each meal and before bedtime. Urine strips every morning and as soon as capillary blood glucose exceeds 2.5 g / L.

– Somogyi effect: the patient with hypoglycemic events usually nocturnal and unnoticed passersby with hyperglycemic rebound with glycosuria (linked to the start of hyperglycemia and late night), urine ketones is related to the induced lipolysis to compensate for the night ketonuria. CAT: reduce the evening insulin dose or increase caloric intake if it is insufficient.

– Glycosylated hemoglobin (HbA1c) integrates the glycemic values ​​of previous 2 to 3 months and is well correlated to the value of fasting glucose (normal 4-6%). Glycemic control is considered satisfactory as HbA1c <7%. The optimal goal is a rate lower than 6.5%.

– The fructosamine assay (glycemic control 2 to 3 weeks) can be useful during pregnancy.

– Annual Review: Triglyceride and cholesterol; creatinine; microalbuminuria or proteinuria of 24 hours; Urinalysis;Resting ECG; fundus (and / or angiography)

– The FO and / or angiography of the eye will be performed every 5 years and in case of anomalies in the FO.

– An arterial Doppler ultrasound of the supra-aortic trunks and lower limbs will realize if clinical abnormalities or after a change in 10 years.

– After 20 years of evolution of diabetes and / or there are other risk factors, it is essential to regularly schedule a stress test (or thallium scintigraphy myographic).

5- Type 2 Diabetes:

– The macrovascular complications are in the foreground

– The risk of developing type 2 diabetes is higher in the group of glucose-intolerant patients (although 30% of them can spontaneously normalize their glucose tolerance).

– The best markers that occurred in a subsequent diabetes fasting glucose, oral glucose post-load glucose and abdominal obesity.

– Multifactorial;

– Genetic factors: Concordance between 60 and 100% among identical twins; the risk for first-degree relatives of a diabetic (type 2) is 40%; polygenic disease

– Metabolic factors: insulin resistance alone does not explain the occurrence of type 2 diabetes, but it characterizes most of the type 2 diabetes with obesity. It aggravates disorders of insulin secretion. Some degree of insulin resistance is found in many situations outside of diabetes (obesity, essential hypertension, large-nancy …).

– This is essentially a muscle insulin on glycogen synthesis. Excessive release of fatty acids from fat cells explains the competition between free fatty acids and glucose.

– Free fatty acids are oxidized priority, resulting in increased production of acetyl CoA which in turn inhibits the enzymes of glycolysis. Muscle power is supplied from the oxidation of fatty acids and muscle glycogen remains intact, which represses glycogen synthase.

– In the liver, There are a stimulation of gluconeogenesis.

– The main clinical factors of insulin resistance are: obesity (android type); abdominal distribution subcutaneous and visceral fat; physical inactivity; age (elderly).

– Hypertension; higher triglyceride levels and lower HDL appear as a result of insulin resistance

– An android fat distribution is defined by a size ratio (waist at the navel) on hip> 1 (> 0.8 in women).

– The muscle fast twitch fibers (type 2) on inulinorésistantes more than slow twitch muscle fibers (type 1). A sedentary lifestyle and aging favor the elevation of muscle fiber type 2.

– Insulin resistance:

* Precedes type 2 diabetes

* Occurs on a genetic susceptibility field

* Reduces muscle glucose utilization

* Increases the hepatic glucose production

* If translated android obesity

* Often accompanied by hypertension, hypertriglyceridemia and hypo-HDL-emia.

– The insulin decreases progressively; it is first on then becomes absolute.

– When one parent is diabetic, the risk to their children is 30%; when both parents are diabetic risk is around 50%.

– Obesity is a source of insulin resistance by decreasing the number of membrane receptors for insulin.

– Only one clinical sign is characteristic of diabetes: necrobiosis lipoidica (large closets with lupus and yellowish skin thinned and atrophic.

– Transitional Insulin: pregnancy (mandatory), surgery, intercurrent infection, progressive complications

– Signs of insulinoréquérence: spontaneous weight loss, cardinal signs, urine ketones.

– The endogenous insulin reserves can be assessed by measurement of C-peptide

– The prescription diet may be enough to control blood sugar

– Overweight -> reduced calorie diet with 25 to 30% of the usual calorie diet (55% carbohydrates, 30% fat, 15% protein). Most of the carbohydrate intake based on carbohydrates

– The practice of physical exercise is an essential part of treatment

– The sulfonylureas (tolbutamide, chlorpropamide, glibenclamide or Daonil®) are first-line command in normal weight patients or with a slight overweight.

– Biguanides (metformin or Glucophage) are first-line command in obese patients

– The blood glucose lowering effect of sulfonamides due to the increase in insulin secretion by direct action on B cells secondary major risk of this family is hypoglycemia.

– Glucagon (if hypoglycemia) is not recommended (inefficient kickback of insullinosécrétion)

– Non-cardioselective beta-blockers (propranolol) mask the first signs of hypoglycemia and prolong their effects

– Contraindications sulphonylurea: pregnancy, severe renal or hepatic impairment, association miconazole PC.

– Biguanides work by increasing peripheral glucose utilization (decreased insulin resistance); therefore they do not cause hypoglycemia. Lactic acidosis is the most serious side effect.

– Acarbose inhibits α-glucosidase (maltase) and delays the intestinal intestinal absorption of starch (reduces peak postprandial hyperglycaemia). Do not cause hypoglycaemia

– Laboratory control: fasting blood glucose and postprandial every 3 months; HbA1c every 3 months (good if <7% and very good if <6.5%).

– Annual Review: triglyceride dosage and cholesterol, creatinine, microalbuminuria or proteinuria of 24 hours, urine culture, resting ECG, a fundus and / or angiography (every 5 years and in case of anomaly at the bottom eye)

– Arterial Doppler ultrasound of the supra-aortic trunks and lower limbs after 10 years or when clinical abnormality.

– The EMG is not necessary because a good neurological examination is largely sufficient.