JOURNAL READING Use of Metabolic Markers To Identify Overweight Individuals Who Are Insulin Resistan

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JOURNAL READINGUse of Metabolic Markers To
Identify Overweight Individuals Who Are Insulin
Resistant

• McLaughlin T, Abbasi F, et al.
• Ann Intern Med 2003139802-809

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Introduction

• Insulin resistance
• Insulin resistance and hyperinsulinemia are
  independent predictors of type 2 DM, essential
  hypertension, and CVD
• Insulin resistance is more common in overweight
  individuals
• Lifestyle interventions such as weight loss and
  exercise may improve insulin sensitivity

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Introduction

• On the other hand
• Not all overweight or obese individuals are
  insulin resistant
• Not all of them have disturbances of glucose or
  lipid metabolism
• Metabolic benefits of weight loss are largely
  confined to overweight or obese individuals with
  these metabolic abnormalities at baseline

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Introduction

• Physicians are reluctant to assign weight control
  programs
• Only 50 provided weight loss counseling
• Weight loss medication is not being used
  appropriately in overweight persons
• Identifying overweight individuals with insulin
  resistance would be useful for targeting them for
  lifestyle interventions

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Introduction

• Direct measures of insulin-mediated glucose
  disposal are cumbersome and not clinically
  practical
• Overweight/insulin resistant persons are at
  increased risk for glucose intolerance and have
  characteristic dyslipidemia
• Measuring these variables might help identify
  insulin resistance

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Introduction

• Markers associated with IR
• Fasting plasma glucose
• Plasma insulin concentration
• Plasma triglyceride
• HDL cholesterol
• Total cholesterol / HDL-C ratio
• Triglyceride / HDL-C ratio
• Also a significant predictor of CVD but less
  commonly used

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Purpose of this study

• To develop a simple clinical approach using
  measurements of plasma glucose, insulin, and
  lipid concentration to identify overweight or
  obese individuals who are insulin resistant and
  at greatest risk for CVD

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Methods

• Subjects 258 overweight or obese individuals
  with BMI ? 25 kg/m2
• Drawn from 490 healthy volunteers
• Without known disease according to their medical
  history
• Not taking any medication that influence insulin
  resistance or lipid metabolism
• Nondiabetic on basis of standard OGTT

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Methods

• Subjects
• Men 127, women 131
• Mean age 50 16 years (19-70 years)
• Mean BMI 29.2 3.2 kg/m2 (25.0-39.1 kg/m2 )
• White 87, Asian American 9, Hispanic 3,
  African American 1

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Methods

• Obtained blood samples for plasma glucose,
  insulin, lipid and lipoprotein
• A modified insulin suppression test was used to
  estimate insulin-mediated glucose disposal
• Highly correlated with euglycemic,
  hyperinsulinemic clamp approach (r gt 0.9)
• After overnight fast, IV catheters are placed in
  patients each arm

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• One arm infused for 180 minutes with
• Somatostatin 250 µg/h
• Insulin 179 µmol/m2 per min
• Glucose 13.3 mmol/m2 per min
• Blood samples collected from other arm
• Every 30 min initially, then q10 min from 150-180
  min to determine steady-state plasma insulin and
  glucose concentrations
• Steady-state plasma insulin concentrations are
  similar for all participants
• Therefore steady-state plasma glucose
  concentration directly measures the ability of
  insulin to mediate glucose disposal

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Methods

• Definition of insulin resistance
• Previous study on 490 healthy persons showed
  continuous variability of insulin-mediated
  glucose disposal
• However, the tertile with the highest
  steady-state plasma glucose developed CVD and
  glucose intolerance or DM to a statistically
  significantly greater degree
• Therefore used the steady-state plasma glucose in
  the upper tertile as operational definition of
  insulin resistance

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Methods

• Logistic regression analysis showed no
  interaction between metabolic markers, sex, and
  menopausal status
• Clinical utility of metabolic markers to identify
  the most insulin-resistant tertile were evaluated
  by receiver-operating characteristic curves
  (relation between true-positive and
  false-positive)

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Methods

• Metabolic markers
• Fasting plasma concentrations of
• Glucose
• Insulin
• Triglyceride, cholesterol, HDL-cholesterol
• Ratios of
• Cholesterol / HDL-C
• Triglyceride / HDL-C

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Methods

• Cut-points diagnostic of the top tertile of
  steady-state plasma glucose were based on
• M ws (1 - w) x p, where w prevalence of
  disease (top tertile steady-state plasma
  glucose), s sensitivity, and p specificity
• The cut-point identified is the value that
  maximizes M, which represents the optimal
  combination of sensitivity and specificity

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Methods

• For comparison, the ability of ATP III metabolic
  syndrome criteria to identify insulin resistance
  was also determined

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Results
50
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TG/HDL-C
Insulin
TG
(false positive rate)
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Results

• Triglyceride / HDL-C ratio, triglyceride level,
  and insulin level were statistically
  significantly better than other markers
• Separate ROC curves for men and pre- and
  postmenopausal women showed no statistically
  significant difference between these subgroups

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Results

• Optimal cut-points to identify insulin resistance
  (using maximum M)
• TG/HDL-C ? 1.8 (SI unit) 3.0 (traditional)
• Triglyceride ? 130 mg/dL (1.47 mmol/L)
• Fasting insulin ? 108 pmol/L

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Discussion

• Fundamental principles of this study
• Not all overweight or obese persons are insulin
  resistant
• metabolic abnormalities that increase CVD risk in
  overweight individuals are seen primarily in
  those with insulin resistance
• insulin resistance or compensatory
  hyperinsulinemia statistically significantly
  increases CVD risk
• Weight loss reduces CVD risk factors, which are
  most pronounced in the insulin-resistant subgroup

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Discussion

• Among the 490 volunteers, gt 50 (258) were
  overweight or obese
• Only 129 of the overweight/obese were identified
  as insulin resistant
• In other words, if all 258 obese or overweight
  persons had lost weight, only 50 would have
  statistically significantly improved insulin
  sensitivity and associated CVD risk factors

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Discussion

• The 17 overweight/obese individuals who were
  insulin sensitive did not have the associated
  metabolic consequences
• Therefore a simple way to identify
  overweight/obese persons who were insulin
  resistant and at greatest risk for CVD would be
  clinically beneficial

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Discussion

• The results of this study demonstrate that
  fasting plasma triglyceride, TG/HDL-C ratio, or
  fasting plasma insulin offers a reasonable
  clinical utility
• Plasma insulin
• Most closely related to insulin resistance
• Previous study also showed fasting plasma insulin
  is significantly correlated with insulin-mediated
  glucose disposal

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• However, clinical utility is hampered by lack of
  standardized insulin assay
• Plasma triglyceride and TG/HDL-C ratio
• Less closely related physiologically to insulin
  resistance
• But sensitivity and specificity similar to that
  of plasma insulin
• Recognized to increase CVD risk
• Sensitivity and specificity also similar to ATP
  III criteria to identify IR individuals
• Thus may be advantageous over others to identify
  IR individuals at risk for CVD

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Discussion

• Limitations of the study
• Study sample primarily white
• Different markers or different cut-points may be
  better predictor of IR in other ethnicities
• Relationship between BMI and metabolic
  derangement may differ
• Sensitivity and specificity of the markers could
  be better
• But using ATP III criteria was even less
  sensitive and only slightly more specific

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Conclusions

• More than 1/2 of U.S. population is overweight or
  obese
• Approximately 1/2 of these have clinically
  significant insulin resistance
• Identifying overweight/obese individuals who are
  insulin resistant could help health care
  professional focus lifestyle interventions on
  such individuals at greatest risk for CVD

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Conclusions

• Using cut-points of plasma triglyceride
  concentration or TG / HDL-C ratio
• Relatively simple
• Is based on changes in lipid metabolism known to
  increase CVD risk
• Seems to be at least as effective as other
  alternatives

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