DIABETES

Introduction and History of the Diabetes Mellitus:

Polyuric diseases are described for over 3500 years. The name “diabetes” derived
from the Greek word for a syphon; the sweet taste of diabetic urine was recognized
at the start of primary millennium, but the epithet “mellitus” (honeyed) was only
added via Rollo within the pendent 18th century. The sugar in diabetic urine was
identified as glucose by Chevreul in the 1815. within the 1840s, Bernard showed
that glucose was normally present in blood, and showed that it had been stored in
the liver (as glycogen) for secretion into the bloodstream during fasting. In 1889,
Minkowski and von Mering reported that pancreatectomy caused severe diabetes
within dog. In 1893, Laguesse counseled to that amount the pancreatic “islets”
described by way of Langerhans among 1869 evolved an indoor secretion up to
expectation systematical glucose metabolism. Diabetes was subdivided on clinical
grounds into diabe` te maigre (lean subjects) and diabe` te gras (obese) by
Lancereaux in 1880, and through 1930s by Falta and Himsworth into insulin-
sensitive and insulin-insensitive types. These classifications were the forerunners
of the etiological classification into type 1 (insulin-dependent) and sort 2 (non-
insulin-dependent) diabetes. Insulin resistance and β-cell failure, the elemental
defects of type 2 diabetes, are detected by many researchers. The “insulin clamp”
method devised by Andres and DeFronzo was the primary accurate technique for
measuring insulin action. type II diabetes of the young was described as a definite
variant of type 2 diabetes by Tattersall in 1974. the varied sorts of diabetic
retinopathy were described in the last half of the 19th century as were the
symptoms of neuropathy. That improved glucose control in both type 1 and sort 2
diabetes was beneficial was proved by the Diabetes Control and Complications
Trial (1993) and therefore the UK Prospective Diabetes Study (1998). Landmarks
within the treatment of complications include photocoagulation for retinopathy
first described by Meyer-Schwickerath; the importance of vital sign control to slow
the progression of nephropathy (demonstrated by Mogensen and Parving); the
introduction of low-dose insulin within the treatment of diabetic ketoacidosis
within the 1970s.

 Relation of Treatment to Arteriosclerosis: Relation of Treatment to

Arteriosclerosis: Mainly due to the hypertension and high levels of
circulating cholesterol and other lipids in diabetic patients, atherosclerosis,
arteriosclerosis, severe coronary heart condition , and multiple
microcirculatory lesions develop much more easily than in normal people.
Indeed, persons who have poorly controlled diabetes throughout childhood
are likely to die of heart condition in early adulthood. within the youth of
diabetes treatment, the tendency was to severely reduce carbohydrates
within the diet to attenuate insulin requirements. This approach kept the
blood glucose from reaching too high A level and attenuated loss of glucose
within the urine, but it didn't prevent many of the abnormalities of
metabolism . Consequently, the present tendency is to allow the patient to
consume an almost normal carbohydrate diet while administering enough
insulin to metabolize the carbohydrates. This approach decreases the speed
of metabolism and depresses the high level of cholesterol within the blood.
Because complications of diabetes like atherosclerosis, increased
susceptibility to infection, diabetic retinopathy, cataracts, hypertension, and
chronic renal disease are closely related to the amount of lipids and glucose
within the blood, most physicians also prescribe lipid-lowering drugs to
assist prevent these disturbances.
  Insulinoma—Hyperinsulinism: Although excessive insulin production
occurs much more rarely than does diabetes, it occasionally can be a
consequence of an adenoma of an islet of Langerhans. About 10 to 15
percent of these adenomas are malignant, and occasionally metastases from
the islets of Langerhans spread throughout the body, causing tremendous
production of insulin by both the primary and metastatic cancers. Indeed,
some of these patients have required more than 1000 grams of glucose
every 24 hours to prevent hypoglycemia.

Insulin Shock and Hypoglycemia: As already emphasized, the central

nervous system normally derives essentially all its the energy from glucose
metabolism, and insulin is not necessary for this use of glucose.

 Diabetic retinopathy: Diabetic retinopathy (DR) is one of the most

common causes of blindness in adults between 30 and 65 years of age in
developed countries. The prevalence of DR increases with duration of
diabetes, and almost all individuals with type 1 diabetes and the majority of
those with type 2 diabetes will have some degree of DR after 20 years. The
pathogenesis, clinical features and management of diabetic retinopathy, as
well as screening and prevention.

Complications of diabetes:
Despite all the treatments now available, the result for patients with diabetes
remains disappointing. Long-term complications of diabetes still cause significant
morbidity and mortality (Boxes 20.35 and 20.36). Excess mortality in diabetes is
caused mainly by large vessel disease, particularly myocardial infarction and
stroke. Macrovascular disease also causes substantial morbidity from myocardial
infarction, stroke, angina, cardiac failure and intermittent claudication. The
pathological changes of atherosclerosis in diabetic patients are almost like those
within the non-diabetic population but occur earlier in life and are more extensive
and severe. Diabetes amplifies the consequences of the opposite major
cardiovascular risk factors: smoking, hypertension and dyslipidaemia. Moreover,
patients with type 2 diabetes are more likely to possess additional cardiovascular
risk factors, which co-segregate with insulin resistance within the metabolic
syndrome (p. 730). Mortality statistics from the USA indicate that cardiovascular
death rates are 1.7 times higher in adults with diabetes aged 20 years or older
compared to adults within the same age bracket who don't have diabetes, while
similar figures for myocardial infarction show a 1.8 times greater rate.
Hospitalisation rates for stroke were 1.5 times higher in adults with diabetes than
in those without diabetes. additionally , 60% of non-traumatic amputations among
people aged 20 years or older were reported to be in people with diabetes. Type 1
diabetes is additionally related to increased cardiovascular risk. Recent data from
Scotland show that the age-adjusted incidence rate ratio for first cardiovascular
event was 3 times higher in women and a couple of 2.3 times higher in the men
with type 1 diabetes compared to those without diabetes.
Genetic predisposition:

Genetic factors are important in type 2 diabetes, as shown by marked differences in

susceptibility in various ethnic groups and by studies in monozygotic twins where
concordance rates for type 2 diabetes approach 100%. However, many genes are
involved and the chance of developing diabetes is also affected very powerfully by
environmental factors. Genome-wide related studies have identified over 70 genes
or gene regions that are related with type 2 diabetes, each exerting a small effect.
Most of the genes known to contribute to risk of type 2 diabetes are involved in β-
cell function or in controlling of cell cycling and turnover, suggesting that changed
regulation of β-cell mass is a key factor. The largest population genetic effect
described to date is seen with variation in TCF7L2; the 10% of population with
two copies of the risk variant for this gene have a nearly twofold increase in the
risk of developing type 2 diabetes. In general, other common variants explain
much lower risk than this, many explaining less than a 10% increase in risk only;
as only about 10% of the genetic variance in type 2 diabetes is explained by these
common genetic variants, this has led some to question the relevance of finding
diabetes genes. However, it should be noted that, within a population, the
distribution of risk variants will vary, with some patients having inherited a high
genetic burden (e.g. more than 40 risk variants) and others having inherited very
few. When studies compare those in the top 20% of this risk band with the lowest
20%, those at highest risk are over 2.5 times more likely to develop diabetes. More
recent insights into the genetics of type 2 diabetes have highlighted how some
genetic variants may be rare and therefore affect only a small proportion of the
population, but have large clinical effects.
GGGGG2 Although not showing an easy pattern of inheritance, type 1 diabetes is
strongly influenced by genetic factors. the connection is complex and, as indicated,
multifactorial. Monozygotic twins have a disease concordance rate of 30–50%,
while dizygotic twins have a concordance of 6–10%. within the USA, the danger
of developing type 1 diabetes is 1 : 20 for those with a first-degree relative,
compared with a 1 : 300 risk within the general population. Children of mothers
with type 1 diabetes have a 1–4% risk of developing type 1 diabetes, but children
of fathers with type 1 diabetes have a tenth risk. Despite this genetic influence, 80–
85% of latest cases present in individuals with no known case history of the
disease. The inheritance of type 1 diabetes is polygenic, with over 20 different
regions of the human genome showing an association with type 1 diabetes risk.