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* Department of Internal Medicine, Faculty of Medicine, University of Indonesia - dr. Cipto Mangunkusumo Hospital.
Jl. Diponegoro no. 71, Jakarta Pusat 10430, Indonesia. ** Department of Internal Medicine, Faculty of Medicine,
University of Indonesia - dr. Cipto Mangunkusumo Hospital & Persahabatan Hospital, Jakarta, Indonesia.
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Vol 42 Number 4 October 2010 Insulin Resistance Profile Among Siblings of Type 2 Diabetes Mellitus
A preliminary, cross sectional study was conducted Characteristics Mean (SD) Median
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Dyah Purnamasari Acta Med Indones-Indones J Intern Med
Table 3. The frequency of metabolic components in insulin of a history of type 2 DM in the father or mother or
resistance group
both at the incidence of insulin resistance can not be
Metabolic components Number of insulin Percentage
in insulin resistance resistance (n=8) (%) viewed because it is not performed genetic analysis.
Central obesity In this research note that in type 2 diabetic
- Yes 8 100.0 subjects with decreased HDL cholesterol, tend to have
- No 0 0
Hypertension
siblings with decreased HDL cholesterol as well.
- Yes 4 50.0 Although the significance is not determined yet, this
- No 4 50.0 possibility supports the findings of De Fronzo that the
Hypocholesterol HDL
- Yes 4 50.0 phenotype picture of insulin resistance is influenced by
- No 4 50.0 several genes that form the background of gene D
Hypertriglyceridemia
- Yes 4 50.0 (Diabetic gene), genes of L (lipid gene), gene H
- No 4 50.0 (hypertension gene), and gene A (atherosclerotic
Hyperglycemia
- Yes 3 37.5
gene).19,24 Individuals who are insulin resistance, with
- No 5 62.5 the influence of the dominant gene D will be type 2
DM, with the dominant influence of the L gene would
have dyslipidemia (hypertriglyceridemia or decreased
DISCUSSION of HDL level), as well as for hypertension and that of
In this study, we examined siblings of diabetic atherosclerosis.15,19
patients aged were 45-55 years old. The average age In addition, although it is not significant, siblings of
of the siblings was 47 years old, despite finding a 38- type 2 DM who relatively have younger onset of type
years-old diabetic patient who has siblings aged 29-34 2 DM (<40 years old) tend to have an average value
years old. Thus, the results achieved in this study are of HOMA-IR higher than those with older onset of
limited to the population or in families with the same type 2 DM. This was previously reported by Tripathy
age range. et al that siblings of type 2 DM whose age is relatively
In this study, the cut-off value of HOMA-IR is 2.04. younger (<44 years) will have siblings with an average
Cut-off values of HOMA-IR ever reported vary value of HOMA-IR higher than those with older onset
widely, but for the high risk population as in this study of type 2 DM (p <0.005).23
have not been reported. Differences in cut-off value The frequency of insulin resistance in all subjects
of HOMA-IR in previous studies reinforce the as a group is 26.67%. In this study, incidence of insulin
perception that insulin resistance is different from one resistance increases with age and is highly found in
population to another population that is likely determined the age group 41-50 years and then decreases with
by other inter-gender, the difference of body fat increasing age most probably caused by the prevalence
distribution between men and women, ethnic and age.21 of bias. Among three quarters of subjects with insulin
In this study, the cut-off value of HOMA-IR is resistance had a BMI >25 kg/m2. This finding is in line
relatively low compared to previous studies (in the with Nasution (2005) who reported the relationship
general population). It is very likely due to the number between BMI with insulin resistance (p = 0.017). With
of subjects that is relatively small.36-38 different approaches, the relationship between IMT,
Tripathy and Vaag (EGIR study) reported that insulin resistance can be seen from the report by Choi
individuals with a family history of diabetes (first et al, which involved 1314 subjects with age >60 years,
degree relative) have a higher insulin resistance and Thomas et al involving 225 Chinese subjects aged
(represented by the average value of HOMA-IR, not 65-74 years. Two studies showed increased BMI with
a cut-off HOMA-IR) than individuals without a HOMA-IR degrees which are grouped into quartiles.25
history of DM.23 The average value of HOMA-IR in In this study, central obesity is highest among the
the group with a family history of DM on a study by other metabolic components. Pranoto et al in Surabaya
Tripathy is 1.21, whereas in this study is 1.60. In this and Adam et al in Makassar also reported that central
study, the frequency of insulin resistance varies within obesity component of metabolic syndrome is most
families between 0-75%. If the effect of genetic commonly found.22,26 However, several other studies
factors being equal on all subjects of the study, showed different results. Nasution reported
significant variations can indicate the strong influence hypertension is a component of the metabolic syndrome
of environment on insulin resistance. While in this study, that most often found in the elderly group (>60 years).
there are several environmental factors which are not These differences are likely influenced by the age range
analyzed, such as diet and exercise habits. Influence studied. In Bali and Pekalongan, a prominent
206
Vol 42 Number 4 October 2010 Insulin Resistance Profile Among Siblings of Type 2 Diabetes Mellitus
component of the metabolic syndrome is a decrease in 4. Axelsen M, Smith U, Eriksson JW, Taskinen M, Jansson P.
HDL cholesterol level and hypertension.27,28 Postprandial hypertriglyceridemia and insulin resistance in
normoglycemic first degree relatives of patients with type 2
Central obesity was also found in all subjects with diabetes. Ann Intern Med. 1999;131:27-31.
normal glucose tolerance and insulin resistance. This 5. Dandona P, Aljada A. A rational approach to pathogenesis
is in line with research conducted by Carr et al who and treatment of type 2 diabetes mellitus, insulin resistance,
reported that abdominal circumference is very good inflammation and atherosclerosis. Am J Cardiol. 2002;90
suppl:27G-33G.
for identifying insulin resistance in subjects with nor-
6. Reusch JEB. Current concepts in insulin resistance, type 2
mal glucose tolerance (p<0.001).29 As explained in the diabetes mellitus and the metabolic syndrome. Am J Cardiol.
literature review, the central role of obesity on meta- 2002;90 suppl:19G-26G.
bolic syndrome considering its function as a source of 7. Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson
FFA, adipokin, adinopektin, TNF and IL-6 that JK. Increased insulin concentration in nondiabetic offspring
of diabetic parents. N Engl J Med. 1988;319:1297-1301.
affect the emergence of insulin resistance.19,29,30 8. Krikftos AD, Greenfield JR, Peake PW, Furler SM, Denver
Increased uric acid was not found on the subject GS, Charlesworth JA. Inflammation, insulin resistance and
of this research, so this parameter is very insensitive adiposity: A study of first degree relatives of type 2 diabetic
to predict the incidence of insulin resistance. subjects. Diab Care. 2004;27:2033-40.
9. DeFronzo RA, Mandarino L, Ferrannini E. Metabolic and
Meanwhile, hypertension, increased triglyceride
molecular pathogenesis of type 2 diabetes mellitus. In:
concentrations, decreased HDL cholesterol concen- DeFronzo RA, et al, eds. International textbook of diabetes
trations and hyperglycemia (fasting blood glucose >110 mellitus. 3rd ed. West Sussex: John Wiley & Sons; 2004. p.
mg/dl) can be used to predict insulin resistance, 389-438.
although not as good as central obesity. 10. Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A,
Goico J. Preservation of pancreatic beta cell function and
Limitations in this study were (1) This study is a prevention of type 2 diabetes by pharmacological treatment
preliminary study with a sample of only 30 people of insulin resistance in high risk Hispanic women. Diabetes.
(seven families) that can not be used to analyze the 2002;51:186-92.
relationship (2) the results of this study can not be used 11. Eriksson JG, Franssila-Kallunki A, Ekstrand A, Saloranta C,
Widen E, Schalin C, et al. Early metabolic defects in person at
to represent high-risk groups in Indonesia, due to the
increased risk for non-insulin-dependent diabetes mellitus. N
strong influence of ethnic factors on the incidence of Engl J Med. 1989;321:337-43.
insulin resistance (3) genetic analysis can not be done 12. Vaag A, Lehtovirta M, Thye-Ronn P, Groop L. Metabolic
so that the genetic role is not clearly visible, and (4) impact of a family history of type 2 diabetes. Results from a
this study did not use a control group (individuals who European multicentre study (EGIR). Diabet Med.
2001;18:533-40.
had no family history of DM) as a comparator so that 13. Vaag A, Henriksen JE, Madsbad S, Holm N, Beck-Nielsen H.
the difference between high risk groups and low risk is Insulin secretion, insulin action and hepatic glucose
not visible. production in identical twins discordant for non-insulin-
dependent diabetes mellitus. J Clin Invest. 1995;95:690-8.
14. Henriksen JE, Levin K, Thye-Ronn P, Alford F, Hother-
CONCLUSION Nielsen O, Holst JJ. Glucose-mediated glucose disposal in
insulin-resistant normoglycemic relatives of type 2 diabetic
The prevalence of insulin resistance among
patients. Diabetes. 2000;49:1209-18.
siblings of type 2 DM in this study was 26.67% with 15. Groop L, Forsblom C, Lehtovirta M, Tuomi T, Karanko S,
the proportion in each family varied between 0-75%. Snissen M. Metabolic consequences of a family history of
Central obesity was the most metabolic component NIDDM (the Botnia Study): Evidence for sex-specific
commonly found. parental effects. Diabetes. 1996;45:1585-93.
16. Vidal PM, Mazoyer E, Bongard V, Gourdy P, Ruidavets JB,
Drouet L. Prevalence of insulin resistance syndrome in south-
western France and its relationship with inflammatory and
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