Insulin status and pancreas cancer

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Hi All,

Higher insulin levels may predict future pancreatic cancer in this study, which

is

good because it is a report of a prospective study and is pdf-available.

It may be of interest in the below that the protein level was significantly

associated with the insulin level in Figure 2. That the association should also

apply to saturated fat may not be too unexpected, but total fat was also

associated

with the level of insulin in the blood.

BMI and weights were associated with the level of insulin, but it may surprise

that

energy consumption was not.

This Week in JAMA

JAMA. 2005;294:2811.

Insulin, Insulin Resistance, and Pancreatic Cancer

Diabetes mellitus and glucose intolerance have been associated with increased

risk

of pancreatic cancer in several studies, but these could be a result of

subclinical

malignancy. Stolzenberg- and colleagues assessed the relationship of

baseline

fasting serum insulin and glucose concentrations to a diagnosis of exocrine

pancreatic cancer 5 or more years later in a prospective case-cohort study of

male

smokers. After adjustment for age, years smoked, and body mass index, the

authors

found that higher prediagnostic fasting serum insulin and insulin resistance

were

related in a dose-response manner to an increased risk of exocrine pancreatic

cancer.

Insulin, Glucose, Insulin Resistance, and Pancreatic Cancer in Male Smokers

Z. Stolzenberg-; Barry I. Graubard; Suresh Chari; Limburg;

Philip R. ; Jarmo Virtamo; Demetrius Albanes

JAMA. 2005;294:2872-2878.

ABSTRACT

Context Obesity, diabetes mellitus, and glucose intolerance have been

associated

with increased pancreatic cancer risk; however, prediagnostic serum insulin

concentration has not been evaluated as a predictor of this malignancy.

Objective To investigate whether prediagnostic fasting glucose and insulin

concentrations and insulin resistance are associated with subsequent incidence

of

exocrine pancreatic cancer in a cohort of male smokers.

Design, Setting, and Participants A case-cohort prospective study within the

Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-1988) cohort of 29

133

male Finnish smokers ages 50 to 69 years. The study included 400 randomly

sampled

subcohort control participants and 169 incident pancreatic cancer cases that

occurred after the fifth year of follow-up. All participants were followed up

through December 2001 (up to 16.7 years of follow-up).

Main Outcome Measures Incident exocrine pancreatic cancer identified from the

Finnish Cancer Registry.

Results After adjusting for age, smoking, and body mass index, higher baseline

fasting serum concentrations of glucose, insulin, and insulin resistance were

positively associated with pancreatic cancer. The presence of biochemically

defined

diabetes mellitus (glucose, 126 mg/dL [6.99 mmol/L]) and insulin concentration

in

the highest vs lowest quartile both showed a significant 2-fold increased risk

(hazard ratio

---

, 2.13; 95% confidence interval [CI], 1.04-4.35; and HR, 2.01;

95%

CI, 1.03-3.93; respectively). There were significant interactions for all the

biomarker exposures by follow-up time, such that the positive associations were

stronger among the cases that occurred more than 10 years after baseline

(highest vs

lowest quartile: glucose, HR, 2.16; 95% CI, 1.05-4.42; P for trend = .02;

insulin,

HR, 2.90; 95% CI, 1.22-6.92; P for trend = .005; and insulin resistance, HR,

2.71;

95% CI, 1.19-6.18; P for trend = .006).

Conclusions These results support the hypothesis that exposure to higher

insulin

concentrations and insulin resistance predicts the risk of exocrine pancreatic

cancer.

.... Table 2. Selected Age-Adjusted Characteristics of Subcohort Control

Participants

by Quartile of Fasting Serum Insulin*

=========================================

Characteristics----Fasting Serum Insulin, Quartile----PTrend

----1 2 3 4----

=========================================

Quartile, microIU/mL 2.05 (1.51-2.58) 3.47 (2.94-4.00) 5.04 (4.52-5.57) 10.22

(9.67-10.77)

------------------------------------------------------------------

Demographics

Age, y 56.6 (55.6-57.4) 56.1 (55.2-57.1) 56.1 (55.1-57.1) 56.7 (55.7-57.7)

..67

Height, cm 173.1 (171.9-174.2) 174.0 (172.8-175.1) 174.4 (173.2-175.5) 173.8

(175.0-172.6) .54

Weight, kg 72.5 (70.4-74.7) 75.9 (73.8-78.1) 82.5 (80.4-84.7) 91.2

(89.0-93.5)

<.001

BMI 24.2 (23.6-24.8) 25.0 (24.4-25.7) 27.1 (26.5-27.8) 30.8 (29.5-30.8) <.001

Primary school education or less 84.0 (75.5-90.0) 75.4 (66.1-82.8) 71.1

(61.6-79.0) 84.3 (75.6-90.3) .66

Living in a city 54.1 (44.3-63.4) 46.4 (37.0 (56.2) 43.6 (34.3-53.4) 38.7

(29.5-48.7) .04

------------------------------------------------------------------

Clinical characteristics

Glucose, mg/dL 94.3 (89.9-98.8) 99.5 (95.1-103.9) 105.3 (100.9-109.7) 115.7

(111.2-120.3) <.001

Insulin resistance (HOMA-IR) 0.48 (0.18-0.77) 0.85 (0.55-1.14) 1.31

(1.02-1.60)

3.14 (2.84-3.44) <.001

------------------------------------------------------------------Medical

history

History of diabetes mellitus 1.0 (0.1-6.7) 1.0 (0.1-6.7) 3.9 (1.5-9.9) 12.2

(7.0-20.5) <.001

Smoking history

Total cigarettes/d 20.6 (19.0-22.1) 20.7 (19.1-21.0) 19.4 (17.8-21.0) 21.3

(19.7-23.0) .57

Years of smoking 35.5 (34.1-36.9) 34.5 (33.1-35.8) 34.1 (32.8-35.5) 35.3

(33.9-36.7) .87

------------------------------------------------------------------

Dietary intake per d^†

Energy, kcal 2862.6 (2696-3029) 2760 (2597-2924) 2782 (2619-2944) 2942

(2775-3110) .32

Protein, g 100.6 (97.8-103.5) 102.5 (99.7-105.3) 106.4 (103.6-109.2) 105.4

(102.5-108.2) .02

Fat, g 98.6 (95.2-101.9) 100.7 (97.4-104.0) 102.8 (99.5-106.0) 104.2

(100.8-107.6) .02

Saturated fat, g 51.6 (48.8-54.5) 52.7 (49.9-55.5) 52.6 (49.9-55.4) 56.5

(53.6-59.4) .01

Carbohydrate, g 308 (299-318) 308 (299-316) 300 (291-309) 301 (292-311) .26

Starch, g 145.4 (138.5-152.3) 146.9 (140.1-153.7) 145.0 (138.3-151.8) 142.8

(135.9-149.8) .49

Free sugars, g 71.4 (65.0-77.7) 69.3 (75.5-63.1) 67.9 (61.7-74.0) 65.0

(58.6-71.4) .16

Sucrose, g 64.4 (58.4-70.3) 61.1 (55.2-67.0) 58.1 (52.2-63.9) 56.8

(50.7-62.8)

..08

Fiber, g 26.1 (24.5-27.7) 25.7 (24.2-27.3) 25.1 (23.5-26.6) 25.3 (23.7-26.9)

..48

Alcohol, g 24.1 (19.4-28.8) 19.6 (14.9-24.2) 16.9 (12.3-21.4) 18.1

(13.4-22.8)

..10

------------------------------------------------------------------

Physical activity

Occupational

Sedentary 8.1 (4.1-15.1) 12.6 (7.5-20.5) 14.5 (8.9-22.8) 13.6 (8.1-22.1)

..29

Light/moderate 41.1 (31.3-51.6) 41.9 (32.3-52.2) 37.0 (27.7-47.3) 34.4

(25.2-44.9) .29

Heavy 11.1 (6.2-19.0) 10.0 (5.5-17.5) 5.9 (2.8-12.3) 5.8 (2.6-12.5) .13

Nonworking 36.1 (27.9-44.2) 32.9 (24.8-41.0) 38.3 (30.3-46.3) 42.0

(33.7-50.3)

..18

Leisure

Sedentary 42.2 (31.9-53.2) 35.9 (26.2-47.0) 40.3 (30.2-51.2) 44.0

(33.6-55.0)

..12

Exercise to keep fit 10.8 (6.0-18.6) 6.9 (3.3-13.8) 2.9 (0.9-8.6) 3.0

(1.0-9.0) .02

Walk, fishing, hunt, gardening 46.9 (37.3-56.7) 56.6 (46.8-65.9) 53.5

(43.9-62.9) 46.7 (37.9-56.7) .64

=========================================

Abbreviations: BMI, body mass index (calculated as weight in kilograms divided

by

height in meters squared); CI, confidence interval; HOMA-IR, Homeostasis Model

Assessment & #8722;Insulin Resistance.

SI conversions: To convert glucose to mmol/L, multiply by 0.0555; insulin to

pmol/L,

multiply by 6.945.

*Generalized linear models and logistic regression, adjusted for age, continuous

factors, and proportions, respectively, were used to calculate means and 95%

CIs.

^†Dietary variables were adjusted for energy, with the exception of alcohol.

Al Pater, PhD; email: old542000@...

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