Prevalence of diabetic complications in fibrocalculous pancreatic diabetic patients and type 2 diabetic patients: A cross-sectional comparative study

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<ul><li><p>anabhan, Gopal Premalatha, Raj Deepa,</p><p>(P= .003), and glycosylated hemoglobin (P= .001). Among subjects with FCPD, systolic blood pressure (P= .013), glycosylated</p><p>Journal of Diabetes and Its Complicatioprevalence of retinopathy, nephropathy, neuropathy, and PVD was similar among FCPD patients and type 2 diabetic patients, but the</p><p>prevalence of CAD was lower among FCPD patients.</p><p>D 2004 Elsevier Inc. All rights reserved.</p><p>Keywords: Fibrocalculous pancreatic diabetes; Type 2 diabetes; Diabetic retinopathy; Coronary artery disease; Peripheral vascular disease; Diabetic</p><p>nephropathy</p><p>1. Introduction secondary to tropical chronic pancreatitis (TCP) (Balak-(P= .010), and duration of diabetes (P= .024) with nephropathy anhemoglobin (P= .021), and duration of diabetes (P&lt; .001) were associated with retinopathy; BMI (P= .057), glycosylated hemoglobin</p><p>d age (P= .011) and BMI (P= .010) with neuropathy. Conclusion: TheMohan Rema, Viswanathan Mohan*</p><p>Madras Diabetes Research Foundation, No. 4, Conran Smith Road, Gopalapuram, Chennai 600 086, India</p><p>Received 17 January 2003; received in revised form 20 May 2003; accepted 17 June 2003</p><p>Abstract</p><p>Objective: To determine the prevalence of diabetes-related complications in subjects with fibrocalculous pancreatic diabetes (FCPD) and</p><p>compare them with subjects with type 2 diabetes mellitus matched for age, sex, and duration of diabetes. Methods: The study group</p><p>comprised of 277 FCPD patients and 277 age, sex, and duration of diabetes-matched type 2 diabetic patients. All the study subjects</p><p>underwent a detailed clinical examination, and fasting blood samples were obtained for biochemical studies. Peripheral Doppler was used for</p><p>diagnosis of peripheral vascular disease (PVD). Vibratory perception threshold (VPT) was determined using biothesiometry for diagnosis of</p><p>neuropathy. Diagnosis of coronary artery disease (CAD) was based on medical history and 12-lead resting ECG. Retinal photographs were</p><p>used for diagnosis of retinopathy using a modified version of Early Treatment Diabetic Retinopathy Study (ETDRS) grading system.</p><p>Results: FCPD patients had lower body mass index (BMI) (P &lt; .001), systolic blood pressure (P&lt; .0001), diastolic blood pressure</p><p>(P &lt; .001), serum cholesterol (P&lt; .001), serum triglyceride (P&lt; .001), and serum creatinine (P &lt; .01) but higher glycosylated hemoglobin</p><p>(P &lt; .001) levels compared to patients with type 2 diabetes. Prevalence of CAD was significantly higher among type 2 diabetic patients</p><p>(11.9%) compared to FCPD patients (5.1%), P &lt; .003. There was no significant difference in the prevalence of other diabetic complications</p><p>between the two study groups (type 2 diabetes vs. FCPD: retinopathy37.2% vs. 30.1%, PVD4.3% vs. 4.7%, Neuropathy25.3% vs.</p><p>20.9%, Nephropathy15.0% vs. 10.1%). Multiple logistic regression analysis revealed the following risk factors for diabetes complications</p><p>among type 2 diabetic subjectsretinopathy: BMI (P= .028), duration of diabetes (P&lt; .001), and glycosylated hemoglobin (P= .026);</p><p>nephropathy: diastolic blood pressure (P= .016) and glycosylated hemoglobin (P= .040); neuropathy: age (P &lt; .001), duration of diabetesKaruna Kanta Barman, Mahesh PadmPrevalence of diabetic complications in fibrocalculous pancreatic</p><p>diabetic patients and type 2 diabetic patients</p><p>A cross-sectional comparative studyFibrocalculous pancreatic diabetes (FCPD) earlier called</p><p>tropical pancreatic diabetes is a unique form of diabetes</p><p>1056-8727/04/$ see front matter D 2004 Elsevier Inc. All rights reserved.</p><p>doi:10.1016/S1056-8727(03)00074-6</p><p>* Corresponding author. Tel.: +91-44-2835-9048; fax: +91-44-2835-</p><p>0935.</p><p>E-mail address: mvdsc@vsnl.com (V. Mohan).</p><p>URL: http://www.mvdsc.org.ns 18 (2004) 264270rishnan, 1987; Mohan &amp; Premalatha, 1997). TCP is a</p><p>nonalcoholic form of chronic pancreatitis predominantly</p><p>affecting young undernourished individuals in developing</p><p>countries (Geevarghese 1968; Mohan et al., 1985). Until the</p><p>1980s, it was believed that long-term diabetes-related com-</p><p>plications were uncommon in all secondary form of diabetes</p><p>including FCPD (Bank, Marks, &amp; Vinik, 1975; Maekawa,</p><p>Ohneda, Kai, Saito, &amp; Koseki, 1978; Sevel, Bristow, Bank,</p></li><li><p>(Mohan &amp; Alberti, 1991).</p><p>etes aFurthermore, there is no data on the prevalence of</p><p>ischemic heart disease, peripheral vascular disease (PVD),</p><p>or nephropathy in FCPD and virtually none comparing the</p><p>various complications in matched subjects with type 2</p><p>diabetes. In this paper, we report on a study of long-term</p><p>complications of diabetes in a large group of FCPD patients</p><p>and compare them with age-, sex-, and duration-matched</p><p>type 2 diabetic patients. To our knowledge, this is the first</p><p>comprehensive study of diabetes-related complications in</p><p>FCPD patients.</p><p>2. Methods and materials</p><p>The study group comprised of 277 consecutive FCPD</p><p>patients who were followed for a minimum period of 5</p><p>years at the M.V. Diabetes Specialities Centre, at Chennai</p><p>(formerly Madras) in southern India. An equal number of</p><p>type 2 diabetic patients matched for age, sex, and duration</p><p>of diabetes registered at our centre were included for</p><p>the study.</p><p>Diagnosis of FCPD was made based on the criteria</p><p>described earlier (Mohan &amp; Alberti, 1991; Mohan &amp; Pre-</p><p>malatha, 1997). Basically, patients classified as FCPD had</p><p>diabetes as defined by the World Health Organization</p><p>(WHO) consulting group criteria (WHO, 1999) and un-</p><p>equivocal evidence of chronic pancreatitis, including history</p><p>of recurrent abdominal pain, pancreatic calculi on plain</p><p>abdominal X-ray, ultrasound evidence of dilated pancreatic</p><p>ducts, and low fecal chymotrypsin levels (</p></li><li><p>Biothesiometry studies were performed by a single</p><p>by the albumin creatinine ratio (ACR) method exceeded</p><p>30 mg/g of creatinine.</p><p>Coronary Artery Disease (CAD) was diagnosed if the</p><p>subject had either myocardial infarction or ischemia. Myo-</p><p>cardial infarction was diagnosed if the subject had any</p><p>previous hospital records documenting treatment for myo-</p><p>cardial infarction and presence of pathological Q waves on</p><p>ECG suggestive of recent or past myocardial infarction.</p><p>Myocardial ischemia was diagnosed if there was unequiv-</p><p>ocal ST/T changes in resting ECG suggestive of ischemia in</p><p>the presence of exertional angina.</p><p>PVD was diagnosed if the ABI was less than 0.9 (Pre-</p><p>malatha, Shanthirani, Deepa, Markowitz, &amp; Mohan, 2000).</p><p>Neuropathy was diagnosed if ankle jerks were absent</p><p>and/or the vibration perception threshold (VPT) at the bony</p><p>prominence of the right big toe was greater than 25 (Young,</p><p>Breddy, Veves, &amp; Boulton, 1994).</p><p>etes and Its Complications 18 (2004) 264270observer in a standardized fashion using a Biothesiometer</p><p>(Biomedical Instrument, Newbury, OH, USA), by measur-</p><p>ing vibratory perception threshold (VPT) on the great toes.</p><p>Subjects were requested to remove their shoes and socks</p><p>and lie supine on a couch for at least 5 min before the</p><p>measurements were made. The foot was kept warm during</p><p>the measurement and as the room was air conditioned, the</p><p>temperature of the room was around 25 jC. The biothesi-ometer tactor, which vibrates at 100 Hz with an amplitude</p><p>proportional to the square of the applied voltage, was</p><p>applied perpendicular to the test site with a constant and</p><p>firm pressure. Subjects were initially familiarized with the</p><p>sensation by holding the tactor against the distal palmar</p><p>surface. VPT was then measured at the distal plantar surface</p><p>of the right great toe. The voltage was slowly increased at</p><p>the rate of 1 V/s, and the VPT was defined as the moment</p><p>when the subject indicated they first felt the vibration. The</p><p>voltage at which this occurred was recorded. Three further</p><p>cycles of readings at each site were performed, recorded,</p><p>and the mean calculated.</p><p>A detailed retinal examination was done by a retinal</p><p>specialist after complete dilatation of eyes using both</p><p>phenylephrine (10%) and tropicamide (1%). Retinal exam-</p><p>ination included indirect and direct ophthalmoscopy. In</p><p>all study subjects, retinal photography was done as de-</p><p>scribed earlier (Rema, Ponnaiya, &amp; Mohan, 1996). Using</p><p>a Topcon VT-50 camera of three fields in both eyes, 45jphotographs were taken. The three photographic fields</p><p>selected were (1) one stereo pair of the posterior pole</p><p>centered on the fovea to show the macula and optic disc,</p><p>(2) one temporal field whose nasal edge touched the</p><p>macula, and (3) the third field was centered as far as</p><p>possible nasally to the optic disc with the disc on the</p><p>edge of the field. The photographs were graded by MR</p><p>using a modified version of the Early Treatment Diabetic</p><p>Retinopathy Study (ETDRS) grading system (ETDRS</p><p>Group, 1991). The study was approved by the institutional</p><p>ethics committee.</p><p>3. Definitions</p><p>Nephropathy was defined as proteinuria z500 mg/day inthe absence of nondiabetic proteinuria. Nondiabetic protein-</p><p>uria was defined as proteinuria in the presence due to</p><p>urinary tract infection or in the absence of retinopathy</p><p>particularly in those with short duration of diabetes. Micro-(DP) and posterior tibial (PT) pressures were measured by</p><p>inflating the BP cuff just above the ankle on both lower</p><p>limbs. The average of DP and PT was taken as ankle</p><p>pressure, and similarly brachial pressure was measured in</p><p>both upper limbs. The ankle/brachial index (ABI) was</p><p>calculated from ankle and brachial pressures. A resting</p><p>12-lead Electrocardiogram was done in all patients.</p><p>K. Kanta Barman et al. / Journal of Diab266albuminuria was diagnosed if the albumin levels estimatedRetinopathy: The retinal photographs were assessed in</p><p>comparison to the ETDRS standard photographs for severity</p><p>of retinopathy as described earlier (ETDRS Group, 1991).</p><p>Briefly, level 10 represents no retinopathy, level 20 through</p><p>50 nonproliferative diabetic retinopathy, and level 60 pro-</p><p>liferative retinopathy.</p><p>3.1. Statistical analysis</p><p>Statistical analysis was done using the SPSS program</p><p>(version 4.0.1) on an IBM PC compatible computer. Stu-</p><p>dents t test was used to compare means between groups.</p><p>Chi-square test was used to compare proportions. P &lt; .05</p><p>was considered to be statistically significant. Multiple</p><p>logistic regression analysis was carried out using diabetic</p><p>complications as the dependant variable, and age, systolic</p><p>BP, diastolic BP, BMI, duration of diabetes, glycosylated</p><p>hemoglobin, serum cholesterol, and serum triglycerides</p><p>were taken as the independent variables. Multiple logistic</p><p>regression analysis was not performed for PVD and</p><p>Table 1</p><p>Clinical and biochemical characteristics of the study population</p><p>Variable</p><p>Type 2 diabetes</p><p>(n= 277)</p><p>FCPD</p><p>(n= 277)</p><p>Males n (%) 197 (71%) 197 (71%)</p><p>Age (years) 48F 10 47F 11Duration of diabetes (years) 11F 7 11F10BMI (kg/m2) 24.8F 3.7 19.0F 3.3*Systolic BP (mm Hg) 135F 15 124F 17*Diastolic BP (mm Hg) 83F 7 80F 8*Fasting plasma glucose (mg/dl) 202F 97 211F 82Glycosylated hemoglobin (%) 9.6F 2.2 10.7F 2.5*Serum cholesterol (mg/dl) 209F 50 174F 44*Serum triglycerides (mg/dl) 202F 140 123F 78*HDL cholesterol (mg/dl) 42F 10 42F 12Serum creatinine (mg/dl) 0.98F 0.7 0.8F 0.3** P &lt; .001 compared to type 2 diabetes.</p></li><li><p>levels compared to patients with type 2 diabetes. There</p><p>4.2. Prevalence of macrovascular complications</p><p>The overall prevalence of CAD was significantly higher</p><p>among type 2 diabetic subjects compared to FCPD</p><p>patients (P &lt; .003). The prevalence of PVD was low in</p><p>both type 2 diabetic subjects (4.3%) and FCPD (4.7%)</p><p>and there was no statistical difference between the two</p><p>groups (Table 2).</p><p>4.3. Prevalence of microvascular complications</p><p>There was no significant difference in the prevalence of</p><p>retinopathy (both nonproliferative and proliferative), neu-</p><p>ropathy, nephropathy, or microalbuminuria between the</p><p>FCPD and type 2 diabetic patients (Table 2).</p><p>Multiple logistic regression analysis revealed glycosy-</p><p>lated hemoglobin [odds ratio (OR) = 1.19, P= .026], dura-</p><p>tion of diabetes (OR = 1.20, P &lt; .001), and BMI (OR = 0.90,</p><p>Table 2</p><p>Prevalence of diabetes complications among the study groups</p><p>Complication</p><p>Type 2</p><p>diabetes</p><p>(n= 277)</p><p>FCPD</p><p>(n= 277)</p><p>P</p><p>value</p><p>CAD</p><p>Infarction n (%) 15 (5.4%) 6 (2.2%) .08</p><p>Ischemia 18 (6.5%) 7 (2.5%) .04</p><p>Overall 33 (11.9%) 13 (5.1%) .003</p><p>PVD n (%) 12 (4.3%) 13 (4.7%) ns</p><p>Retinopathy n (%)</p><p>Nonproliferative diabetic retinopathy 87 (31.4%) 90 (32.9%) ns</p><p>Proliferative diabetic retinopathy 16 (5.8%) 10 (3.6%)</p><p>Overall 103 (37.2%) 100 (36.1%)</p><p>Neuropathy n (%) 70 (25.3%) 58 (20.9%) ns</p><p>Nephropathy n (%) 42 (15.0%) 30 (10.1%) ns</p><p>Microalbuminuria n (%) 65 (23.5%) 73 (26.4%) ns</p><p>K. Kanta Barman et al. / Journal of Diabetes and Its Complications 18 (2004) 264270 267was no significant difference in fasting plasma glucose and</p><p>HDL cholesterol levels among the study groups.CAD owing to small numbers of study subjects with</p><p>these complications.</p><p>4. Results</p><p>4.1. Clinical features of the study population</p><p>Table 1 shows the clinical and biochemical character-</p><p>istics of study population. Seventy-one percent of the study</p><p>population were males. The FCPD patients had lower BMI</p><p>(P &lt; .001), systolic blood pressure (P &lt; .001), diastolic</p><p>blood pressure (P &lt; .001), serum cholesterol (P &lt; .001),</p><p>serum triglyceride levels (P &lt; .001), and serum creatinine</p><p>(P &lt; .01) but higher glycosylated hemoglobin (P &lt; .001)Table 3</p><p>Prevalence of complications among subjects with DM secondary to chronic panc</p><p>References n Country Age</p><p>Duration of</p><p>diabetes HbA1c</p><p>Okuno et al.,</p><p>1990</p><p>649 DM=296 Japan &lt; 10 years</p><p>in 80% of</p><p>patients</p><p>Levitt et al.,</p><p>1995</p><p>30 South</p><p>Africa</p><p>48F 1.9 8 (133) 10.4%(6.223.</p><p>Gullo et al.,</p><p>1990</p><p>40 Italy 49.2 + 7.9 7.9F 5.5 8.8F 1</p><p>Larsen et al.,</p><p>1978</p><p>25 Denmark 39F 11 10F 6 7.4 + 1.</p><p>Briani et al.,</p><p>1988</p><p>86 Italy 52F 9.9 12.4 + 6.8 7.3F 1</p><p>Present</p><p>study</p><p>277 India 47F 11 11F10 10.7F 2</p><p>CADCoronary artery disease, PVDperipheral vascular disease, CAPchro</p><p>chronic pancreatitis, CPchronic pancreatitis, FCPDfibrocalculous pancreaticP= .028) to be associated with retinopathy in type 2 diabetic</p><p>patients. Among subjects with FCPD, in addition to dura-</p><p>tion of diabetes (OR = 1.21, P &lt; .001) and glycosylated</p><p>hemoglobin (OR = 1.21, P= .021), systolic blood pressure</p><p>(OR = 1.04, P= .013) also showed a strong association.</p><p>The risk factors for nephropathy among type 2 diabetic</p><p>subjects were glycosylated hemoglobin (OR = 1.25,</p><p>P= .040) and diastolic blood pressure (OR = 1.07, P=</p><p>.016). In subjects with FCPD, glycosylated hemoglobin</p><p>(OR = 1.31, P= .010) and duration of diabetes (OR = 1.10,</p><p>P= .024) were the risk factors for nephropathy.</p><p>Age showed a strong association with neuropathy in both</p><p>FCPD (OR= 1.05, P= .011) and type 2 diabetic (OR = 1.08,</p><p>P &lt; .001) subjects. In addition to age in type 2 diabetes,</p><p>duration of diabetes (OR= 1.10, P= .003) and glycosylated</p><p>hemoglobin (OR = 1.36, P= .001) were associated with</p><p>neuropathy. BMI (OR = 0.86, P= .010) showed a negative</p><p>association with neuropathy in FCPD patients.</p><p>reatitis</p><p>Retinopathy</p><p>(%)</p><p>Nephropathy</p><p>(%)</p><p>Neuropathy</p><p>(%)</p><p>CAD</p><p>(%)</p><p>PVD</p><p>(%)</p><p>Type of</p><p>diabetes</p><p>33 21.0 36.3 CAP,</p><p>CCP,</p><p>OCP</p><p>4)</p><p>33.3 23 CAP</p><p>.9 47.5 CP</p><p>2 20 18.5 Insulin</p><p>requiring</p><p>CP</p><p>.2 37 23.8 CP</p><p>.5 36.1 10.1 20.9 5.8 4.7 FCPD</p><p>nic alcoholic pancreatitis, CCPchronic calcific pancrea...</p></li></ul>

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