talk about every thing releated to diabetes

1. Diabetes
TYPE I AND II
SYMPTOMS , DIAGNOSIS , TREATMENT , COMPLICATIONS , OBECITY

2. Overview
► Diabetes mellitus (diabetes) is not one disease but rather is a
heterogeneous group of multifactorial, primarily polygenic syndromes
characterized by an elevated fasting blood glucose (FBG) caused by a
relative or absolute deficiency in insulin. Over 29 million people in the
United States (~9% of the population) have diabetes. Of this number, ~8
million are as yet undiagnosed. Diabetes is the leading cause of adult
blindness and amputation and a major cause of renal failure, nerve
damage, heart attacks, and strokes. Most cases of diabetes mellitus
can be separated into two groups (Fig. 25.1), type 1 ([T1D] formerly
called insulin-dependent diabetes mellitus) and type 2 ([T2D] formerly
called non– insulin-dependent diabetes mellitus). The incidence and
prevalence of T2D is increasing because of the aging of the U.S.
population and the increasing prevalence of obesity and sedentary
lifestyles (see p. 349). The increase in children with T2D is particularly
disturbing.

4. TYPE 1

5. Type I

6. Diagnosis
► The onset of T1D is typically during childhood or puberty, and
symptoms develop suddenly. Individuals with T1D can usually be
recognized by the abrupt appearance of polyuria (frequent
urination), polydipsia (excessive thirst), and polyphagia (excessive
hunger), often triggered by physiologic stress such as an infection.
These symptoms are usually accompanied by fatigue and weight
loss. The diagnosis is confirmed by a FBG ≥126 mg/dl (normal is 70–
99). [Note: Fasting is defined as no caloric intake for at least 8 hours.]
A FBG of 100–125 mg/dl is categorized as an impaired FBG.
Individuals with impaired FBG are considered prediabetic and are
at increased risk for developing T2D. Diagnosis can also be made on
the basis of a nonfasting (random) blood glucose level >200 mg/dl
or a glycated hemoglobin (see p. 340) concentration ≥6.5 mg/dl
(normal is

8. The metabolic abnormalities of T1D result from a deficiency of insulin that profoundly affects metabolism in three tissues: liver,
skeletal muscle, and white adipose
► Hyperglycemia and ketonemia: Elevated levels of blood glucose and
ketone bodies are the hallmarks of untreated T1D (see Fig. 25.3).
Hyperglycemia is caused by increased hepatic production of
glucose via gluconeogenesis, combined with diminished peripheral
utilization (muscle and adipose tissue have the insulin-regulated
glucose transporter GLUT-4; see p. 97). Ketonemia results from
increased mobilization of fatty acids (FA) from triacylglycerol (TAG) in
adipose tissue, combined with accelerated hepatic FA β-oxidation
and synthesis of 3- hydroxybutyrate and acetoacetate (ketone
bodies; see p. 196). [Note: Acetyl coenzyme A from β-oxidation is the
substrate for ketogenesis and the allosteric activator of pyruvate
carboxylase, a gluconeogenic enzyme.] Diabetic ketoacidosis (DKA),
a type of metabolic acidosis caused by an imbalance between
ketone body production and use, occurs in 25%–40% of those newly
diagnosed with T1D and may recur if the patient becomes ill (most
commonly with an infection) or does not comply with therapy. DKA is
treated by replacing fluid and electrolytes and administering short-
acting insulin to gradually correct hyperglycemia without
precipitating hypoglycemia

9. ► Hypertriacylglycerolemia: Not all of the FA
flooding the liver can be disposed of
through oxidation and ketone body
synthesis. These excess FA are converted to
TAG, which are packaged and secreted in
very-lowdensity lipoproteins ([VLDL] see p.
230). Chylomicrons rich in dietary TAG are
secreted by the intestinal mucosal cells
following a meal (see p. 227). Because
lipoprotein TAG degradation catalyzed by
lipoprotein lipase in the capillary beds of
adipose tissue (see p. 228) is low in diabetes
(synthesis of the enzyme is decreased when
insulin levels are low), the plasma
chylomicron and VLDL levels are elevated,
resulting in hypertriacylglycerolemia

10. Treatment
► Individuals with T1D must rely on exogenous insulin
delivered subcutaneously (subq) either by periodic
injection or by continuous pumpassisted infusion to
control the hyperglycemia and ketonemia. Two types
of therapeutic injection regimens are currently used,
standard and intensive
► Standard treatment is typically two to three daily
injections of recombinant human insulin. Mean blood
glucose levels obtained are typically 225–275 mg/dl,
with a glycated hemoglobin (HbA1c) level
► In contrast to standard therapy, intensive treatment
seeks to more closely normalize blood glucose through
more frequent monitoring and subsequent injections of
insulin, typically ≥4 times a day. Mean blood glucose
levels of 150 mg/dl can be achieved, with HbA1c ~7%
of the total hemoglobin

11. Hypoglycemia
► Hypoglycemia caused by excess insulin is the most common
complication of insulin therapy, occurring in >90% of patients.
The frequency of hypoglycemic episodes, seizures, and coma is
particularly high with intensive treatment regimens designed to
achieve tight control of blood glucose (Fig. 25.5). In normal
individuals, hypoglycemia triggers a compensatory secretion of
counterregulatory hormones, most notably glucagon and
epinephrine, which promote hepatic production of glucose
(see p. 315). However, patients with T1D also develop a
deficiency of glucagon secretion. This defect occurs early in the
disease and is almost universally present 4 years after diagnosis.
Therefore, these patients rely on epinephrine secretion to
prevent severe hypoglycemia. However, as the disease
progresses, T1D patients show diabetic autonomic neuropathy
and impaired ability to secrete epinephrine in response to
hypoglycemia. The combined deficiency of glucagon and
epinephrine secretion creates a symptom-free condition
sometimes called “hypoglycemia unawareness.”

12. TYPE 2
► T2D is the most common form of the disease, afflicting >90% of
the U.S. population with diabetes. [Note: American Indians,
Alaskan Natives, Hispanic and Latino Americans, African
Americans, and Asian Americans have the highest
prevalence.] Typically, T2D develops gradually without
obvious symptoms. The disease is often detected by routine
screening tests. However, many individuals with T2D have
symptoms of polyuria and polydipsia of several weeks’
duration. Polyphagia may be present but is less common.
Patients with T2D have a combination of insulin resistance and
dysfunctional β cells (Fig. 25.6) but do not require insulin to
sustain life. However, in >90% of these patients, insulin
eventually will be required to control hyperglycemia and keep
HbA1c
► T2D is the most common form of the disease, afflicting >90% of
the U.S. population with diabetes. [Note: American Indians,
Alaskan Natives, Hispanic and Latino Americans, African
Americans, and Asian Americans have the highest
prevalence.] Typically, T2D develops gradually without
obvious symptoms. The disease is often detected by routine
screening tests. However, many individuals with T2D have
symptoms of polyuria and polydipsia of several weeks’
duration. Polyphagia may be present but is less common.
Patients with T2D have a combination of insulin resistance and
dysfunctional β cells (Fig. 25.6) but do not require insulin to
sustain life. However, in >90% of these patients, insulin
eventually will be required to control hyperglycemia and keep
HbA1c

14. Insulin Resistance
Insulin resistance is the decreased ability of target tissues, such as the liver, white
adipose, and skeletal muscle, to respond properly to normal (or elevated)
circulating concentrations of insulin. For example, insulin resistance is
characterized by increased hepatic glucose production, decreased glucose
uptake by muscle and adipose tissue, and increased adipose lipolysis with
production of free fatty acids (FFA).

15. Insulin resistance and obesity
► Although obesity is the most common cause of insulin resistance and increases
the risk of T2D, most people with obesity and insulin resistance do not develop
diabetes. In the absence of a defect in β-cell function, obese individuals can
compensate for insulin resistance with elevated levels of insulin. For example,
Figure 25.7A shows that insulin secretion is two to three times higher in obese
subjects than it is in lean individuals. This higher insulin concentration
compensates for the diminished effect of the hormone (as a result of insulin
resistance) and produces blood glucose levels similar to those observed in lean
individuals

16. Insulin resistance and type 2
diabetes
► Insulin resistance alone will not lead to T2D.
Rather, T2D develops in insulin-resistant
individuals who also show impaired β-cell
function. Insulin resistance and subsequent
risk for the development of T2D is commonly
observed in individuals who are obese,
physically inactive, or elderly and in the 3%–
5% of pregnant women who develop
gestational diabetes. These patients are
unable to sufficiently compensate for insulin
resistance with increased insulin release.
Figure 25.8 shows the time course for the
development of hyperglycemia and the loss
of β-cell function

17. . . Causes of insulin resistanceuses
of insulin resistance
► Insulin resistance increases with weight gain and decreases with weight loss, and
excess adipose tissue (particularly in the abdomen) is key in the development of
insulin resistance. Adipose is not simply an energy storage tissue, but also a
secretory tissue. With obesity, there are changes in adipose secretions that result
in insulin resistance (Fig. 25.9). These include secretion of proinflammatory
cytokines such as interleukin 6 and tumor necrosis factor-α by activated
macrophages (inflammation is associated with insulin resistance); increased
synthesis of leptin, a protein with proinflammatory effects (see p. 353 for
additional effects of leptin); and decreased secretion of adiponectin (see p.
350), a protein with anti-inflammatory effects. The net result is chronic, low-grade
inflammation. One effect of insulin resistance is increased lipolysis and
production of FFA (see Fig. 25.9). FFA availability decreases use of glucose,
contributing to hyperglycemia, and increases ectopic deposition of TAG in liver
(hepatic steatosis). [Note: Steatosis results in nonalcoholic fatty liver disease
(NAFLD). If accompanied by inflammation, a more serious condition,
nonalcoholic steatohepatitis (NASH), can develop.] FFA also have a
proinflammatory effect. In the long term, FFA impair insulin signaling. [Note:
Adiponectin increases FA β-oxidation (see p. 349). Consequently, a decrease in
this adipocyte protein contributes to FFA availability.

19. Treatment
► The goal in treating T2D is to maintain blood glucose concentrations
within normal limits and to prevent the development of long-term
complications. Weight reduction, exercise, and medical nutrition
therapy (dietary modifications) often correct the hyperglycemia of
newly diagnosed T2D. Oral hypoglycemic agents, such as
metformin (decreases hepatic gluconeogenesis), sulfonylureas
(increase insulin secretion; see p. 310), thiazolidinediones (decrease
FFA levels and increase peripheral insulin sensitivity), α-glucosidase
inhibitors (decrease absorption of dietary carbohydrate), and SGLT
inhibitors (decrease renal reabsorption of glucose), or subq insulin
therapy may be required to achieve satisfactory plasma glucose
levels. [Note: Bariatric surgery in morbidly obese individuals with T2D
has been shown to result in disease remission in most patients.
Remission may not be permanent.