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Jurnal 10
Jurnal 10
Jurnal 10
of the b-cells of the pancreas. Markers of C-peptide. Immune-mediated diabetes Type 2 diabetes (ranging from
the immune destruction of the b-cell in- commonly occurs in childhood and ado- predominantly insulin resistance
clude islet cell autoantibodies, autoanti- lescence, but it can occur at any age, even with relative insulin deficiency to
bodies to insulin, autoantibodies to GAD in the 8th and 9th decades of life. predominantly an insulin secretory
(GAD65), and autoantibodies to the ty- Autoimmune destruction of b-cells defect with insulin resistance)
rosine phosphatases IA-2 and IA-2b. has multiple genetic predispositions and This form of diabetes, which accounts for
One and usually more of these autoanti- is also related to environmental factors ;90–95% of those with diabetes, previ-
bodies are present in 85–90% of individ- that are still poorly defined. Although pa- ously referred to as non–insulin-depen-
uals when fasting hyperglycemia is tients are rarely obese when they present dent diabetes, type 2 diabetes, or adult-
initially detected. Also, the disease has with this type of diabetes, the presence of onset diabetes, encompasses individuals
strong HLA associations, with linkage to obesity is not incompatible with the diag- who have insulin resistance and usually
the DQA and DQB genes, and it is influ- nosis. These patients are also prone to have relative (rather than absolute) insu-
enced by the DRB genes. These HLA-DR/ other autoimmune disorders such as lin deficiency At least initially, and often
DQ alleles can be either predisposing or Graves’ disease, Hashimoto’s thyroiditis, throughout their lifetime, these individu-
protective. Addison’s disease, vitiligo, celiac sprue, als do not need insulin treatment to sur-
In this form of diabetes, the rate of autoimmune hepatitis, myasthenia gravis, vive. There are probably many different
b-cell destruction is quite variable, being and pernicious anemia. causes of this form of diabetes. Although
rapid in some individuals (mainly infants Idiopathic diabetes. Some forms of type the specific etiologies are not known, au-
and children) and slow in others (mainly 1 diabetes have no known etiologies. toimmune destruction of b-cells does not
adults). Some patients, particularly chil- Some of these patients have permanent occur, and patients do not have any of the
dren and adolescents, may present with insulinopenia and are prone to ketoaci- other causes of diabetes listed above or
ketoacidosis as the first manifestation of dosis, but have no evidence of autoim- below.
the disease. Others have modest fasting munity. Although only a minority of Most patients with this form of di-
hyperglycemia that can rapidly change patients with type 1 diabetes fall into abetes are obese, and obesity itself causes
to severe hyperglycemia and/or ketoaci- this category, of those who do, most are of some degree of insulin resistance. Patients
dosis in the presence of infection or other African or Asian ancestry. Individuals who are not obese by traditional weight
stress. Still others, particularly adults, with this form of diabetes suffer from criteria may have an increased percentage
may retain residual b-cell function suffi- episodic ketoacidosis and exhibit varying of body fat distributed predominantly in
cient to prevent ketoacidosis for many degrees of insulin deficiency between the abdominal region. Ketoacidosis sel-
years; such individuals eventually be- episodes. This form of diabetes is strongly dom occurs spontaneously in this type of
come dependent on insulin for survival inherited, lacks immunological evidence diabetes; when seen, it usually arises in
and are at risk for ketoacidosis. At this for b-cell autoimmunity, and is not HLA association with the stress of another
latter stage of the disease, there is little associated. An absolute requirement for illness such as infection. This form of
or no insulin secretion, as manifested by insulin replacement therapy in affected diabetes frequently goes undiagnosed for
low or undetectable levels of plasma patients may come and go. many years because the hyperglycemia
develops gradually and at earlier stages is forms result from mutations in other tran- With the exception of that caused by
often not severe enough for the patient to scription factors, including HNF-4a, cancer, damage to the pancreas must be
notice any of the classic symptoms of HNF-1b, insulin promoter factor (IPF)- extensive for diabetes to occur; adreno-
diabetes. Nevertheless, such patients are 1, and NeuroD1. carcinomas that involve only a small
at increased risk of developing macro- Point mutations in mitochondrial portion of the pancreas have been associ-
vascular and microvascular complica- DNA have been found to be associated ated with diabetes. This implies a mech-
tions. Whereas patients with this form of with diabetes and deafness The most anism other than simple reduction in
diabetes may have insulin levels that common mutation occurs at position b-cell mass. If extensive enough, cystic fi-
appear normal or elevated, the higher 3,243 in the tRNA leucine gene, leading brosis and hemochromatosis will also
blood glucose levels in these diabetic to an A-to-G transition. An identical damage b-cells and impair insulin secre-
patients would be expected to result in lesion occurs in the MELAS syndrome tion. Fibrocalculous pancreatopathy may
even higher insulin values had their b-cell (mitochondrial myopathy, encephalopa- be accompanied by abdominal pain radi-
function been normal. Thus, insulin se- thy, lactic acidosis, and stroke-like syn- ating to the back and pancreatic calcifica-
cretion is defective in these patients and drome); however, diabetes is not part of tions identified on X-ray examination.
insufficient to compensate for insulin re- this syndrome, suggesting different phe- Pancreatic fibrosis and calcium stones
Table 1dEtiologic classification of diabetes mellitus have HLA and immune markers charac-
teristic of type 1 diabetes. In addition,
I. Type 1 diabetes (b-cell destruction, usually leading to absolute insulin deficiency)
A. Immune mediated coxsackievirus B, cytomegalovirus, ade-
B. Idiopathic novirus, and mumps have been impli-
II. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency cated in inducing certain cases of the
to a predominantly secretory defect with insulin resistance) disease.
III. Other specific types
A. Genetic defects of b-cell function
Uncommon forms of immune-mediated
1. Chromosome 12, HNF-1a (MODY3) diabetes. In this category, there are two
2. Chromosome 7, glucokinase (MODY2) known conditions, and others are likely
3. Chromosome 20, HNF-4a (MODY1) to occur. The stiff-man syndrome is an
4. Chromosome 13, insulin promoter factor-1 (IPF-1; MODY4) autoimmune disorder of the central ner-
5. Chromosome 17, HNF-1b (MODY5)
6. Chromosome 2, NeuroD1 (MODY6) vous system characterized by stiffness of
7. Mitochondrial DNA the axial muscles with painful spasms.
8. Others Patients usually have high titers of the
B. Genetic defects in insulin action GAD autoantibodies, and approximately
1. Type A insulin resistance
Table 2dCategories of increased risk for abdominal or visceral obesity), dyslipide- communication). Finally, evidence from
diabetes* mia with high triglycerides and/or low the Diabetes Prevention Program (DPP),
FPG 100 mg/dl (5.6 mmol/l) to 125 mg/dl (6.9
HDL cholesterol, and hypertension. wherein the mean A1C was 5.9% (SD
mmol/l) [IFG]
Structured lifestyle intervention, aimed 0.5%), indicates that preventive interven-
2-h PG in the 75-g OGTT 140 mg/dl (7.8
at increasing physical activity and pro- tions are effective in groups of people with
mmol/l) to 199 mg/dl (11.0 mmol/l) [IGT]
ducing 5–10% loss of body weight, and A1C levels both below and above 5.9%
A1C 5.7–6.4%
certain pharmacological agents have been (9). For these reasons, the most appropri-
demonstrated to prevent or delay the de- ate A1C level above which to initiate pre-
*For all three tests, risk is continuous, extending
below the lower limit of the range and becoming velopment of diabetes in people with IGT; ventive interventions is likely to be
disproportionately greater at higher ends of the the potential impact of such interventions somewhere in the range of 5.5–6%.
range. to reduce mortality or the incidence of As was the case with FPG and 2-h PG,
cardiovascular disease has not been dem- defining a lower limit of an intermediate
onstrated to date. It should be noted that category of A1C is somewhat arbitrary,
diabetes has led to more type 2 diabetes in the 2003 ADA Expert Committee report as the risk of diabetes with any measure
women of childbearing age, the number of reduced the lower FPG cut point to define or surrogate of glycemia is a continuum,
practice, a large portion of the population that when a test whose result was above Table 4dScreening for and diagnosis of
with type 2 diabetes remains unaware of the diagnostic threshold is repeated, the GDM
their condition. Thus, it is conceivable second value will be below the diagnostic Perform a 75-g OGTT, with plasma glucose
that the lower sensitivity of A1C at the cut point. This is least likely for A1C, measurement fasting and at 1 and 2 h, at
designated cut point will be offset by the somewhat more likely for FPG, and most 24-28 of weeks gestation in women not
test’s greater practicality, and that wider likely for the 2-h PG. Barring a laboratory previously diagnosed with overt diabetes.
application of a more convenient test error, such patients are likely to have test The OGTT should be performed in the
(A1C) may actually increase the number results near the margins of the threshold morning after an overnight fast of at least
of diagnoses made. for a diagnosis. The healthcare profes- 8 h.
Further research is needed to better sional might opt to follow the patient The diagnosis of GDM is made when any of the
characterize those patients whose glyce- closely and repeat the testing in 3–6 following plasma glucose values are
mic status might be categorized differ- months. exceeded
ently by two different tests (e.g., FPG and The decision about which test to use c Fasting: $92 mg/dl (5.1 mmol/l)
A1C), obtained in close temporal approx- to assess a specific patient for diabetes c 1 h: $180 mg/dl (10.0 mmol/l)
imation. Such discordance may arise from should be at the discretion of the health c 2 h: $153 mg/dl (8.5 mmol/l)