Diabetic nephropathy,clinically The earliest manifestation is the appearance of small amounts of albumin in the urine (> 30 but < 300 mg/day-( microalbuminuria). Without specific interventions, some patients will develop overt nephropathy with macroalbuminuria (excretion of more than 300 mg/day) over the succeeding 10 to 15 years,

5. Ocular Complications of Diabetes: - DM currently is the fourth leading cause of acquired blindness in the United States and visual impairment, and blindness, is one of the more feared consequences of long-standing DM.

-Retinopathy, the most common pattern, consists of changes that are considered by many ophthalmologists to be virtually diagnostic of the disease

Diabetic Neuropathy.: - The most frequent pattern of involvement is that of a peripheral, symmetric neuropathy of the lower extremities affecting motor and sensory nerves particularly the latter and other forms include

- Autonomic neuropathy produces disturbances in bowel and bladder function and sometimes sexual impotence

Clinical Features of Type 1 DM - In the initial 1 or 2 years after manifestation of overt type 1 diabetes ( "honeymoon period"), exogenous insulin requirements may be minimal to none

because of residual ongoing endogenous insulin secretion but thereafter the beta cell reserve is exhausted and insulin requirements increase dramatically

- The onset is marked by polyuria, polydipsia, polyphagia, a. The hyperglycemia exceeds the renal threshold for reabsorption, and glycosuria induces an osmotic diuresis and polyuria.

b. The obligatory renal water loss combined with the hyperosmolarity tends to deplete intracellular water, triggering the thirst centers of the brain and this generates intense thirst (polydipsia).

c. Deficiency of insulin leads to catabolism of proteins and fats which tends to induce a negative energy balance, which in turn leads to increasing appetite (polyphagia)

- Despite the increased appetite, catabolic effects prevail , resulting in weight loss and muscle weakness

Acute complication of type 1 is Diabetic ketoacidosis - The plasma glucose usually is in the range of 500 to 700 mg/dL as a result of absolute insulin deficiency and unopposed effects of epinephrine and glucagon

1. The marked hyperglycemia causes an osmotic diuresis and dehydration characteristic of the ketoacidotic state

- Insulin deficiency leads to excessive breakdown of adipose stores , giving rise to increased FFAs which are oxidized by the liver to produce ketones a source of energy for consumption by brain. .

- The rate at which ketones are formed may exceed the rate at which they can be used by peripheral tissues, leading to ketonemia and ketonuria

-and if the urinary excretion of ketones is diminished by dehydration, the accumulating ketones decrease pH, resulting in metabolic ketoacidosis

Note Glycemic control is assessed clinically by measuring the percentage of glycosylated hemoglobin, also known as HbA1C, which is formed by non-enzymatic addition of glucose moieties to hemoglobin in red cells.

- HbA1C is a measure of glycemic control over long periods of time (2 to 3 months) and is relatively unaffected by day-to-day Variations and an HbA1C below 7% is taken as evidence of tight glycemic control,

IV.The Adrenal gland

I. Adrerenocortical Hyperfunction (Hyperadrenalism) 1 I. Adrerenocortical Hyperfunction (Hyperadrenalism) 1. Hypercortisolism (Cushing Syndrome) - In clinical practice, most cases are caused by the administration of exogenous glucocorticoids (Iatrogenic) - The remaining cases are endogenous and caused by one of the following

a. Hypertension and weight gain are early manifestations. Clinical Manifestations a. Hypertension and weight gain are early manifestations. b. With time, truncal obesity, "moon facies,“ accumulation of fat in the posterior neck and back ("buffalo hump") ,

c. Glucocorticoids induce gluconeogenesis with resultant hyperglycemia, glucosuria, and polydipsia . The catabolic effects on proteins cause loss of collagen and resorption of bone and bone resorption results in the osteoporosis, susceptibility to fractures

e. The skin is thin, fragile, and easily bruised; cutaneous striae are particularly common in the abdominal area g. Patients are at increased risk for a variety of infections. h. Hirsutism and menstrual abnormalities

A. Primary hypothalamic-pituitary diseases associated with hypersecretion of ACTH (Called Cushing disease) Accounts for 70% of cases of spontaneous, endogenous Cushing syndrome .

d. Decreased mineralocorticoid (aldosterone) activity in patients with primary adrenal insufficiency results in potassium retention and sodium loss , with consequent - hyperkalemia, hyponatremia, volume depletion, and hypotension, - In secondary hypoadrenalism is characterized by deficient cortisol and androgen output but normal or near-normal aldosterone synthesis

. - Hypoglycemia occasionally may occur as a result of glucocorticoid deficiency and impaired gluconeogenesis. - Stresses such as infections, trauma, or surgical procedures in affected patients may precipitate an acute adrenal crisis, manifested by a. intractable vomiting,and abdominal pain, b. Hypotension, coma, and vascular collapse. - Death follows rapidly unless corticosteroids are replaced immediately. .