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Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study (Diabetes Metab J 2021;45:675-83)
Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin
Diabetes Metab J. 2022;46(1):162-163.   Published online January 27, 2022
DOI: https://doi.org/10.4093/dmj.2021.0331
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Original Articles
Drug/Regimen
Article image
Effects of Teneligliptin on HbA1c levels, Continuous Glucose Monitoring-Derived Time in Range and Glycemic Variability in Elderly Patients with T2DM (TEDDY Study)
Ji Cheol Bae, Soo Heon Kwak, Hyun Jin Kim, Sang-Yong Kim, You-Cheol Hwang, Sunghwan Suh, Bok Jin Hyun, Ji Eun Cha, Jong Chul Won, Jae Hyeon Kim
Diabetes Metab J. 2022;46(1):81-92.   Published online June 16, 2021
DOI: https://doi.org/10.4093/dmj.2021.0016
  • 9,076 View
  • 461 Download
  • 5 Web of Science
  • 5 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To evaluate the effects of teneligliptin on glycosylated hemoglobin (HbA1c) levels, continuous glucose monitoring (CGM)-derived time in range, and glycemic variability in elderly type 2 diabetes mellitus patients.
Methods
This randomized, double-blinded, placebo-controlled study was conducted in eight centers in Korea (clinical trial registration number: NCT03508323). Sixty-five participants aged ≥65 years, who were treatment-naïve or had been treated with stable doses of metformin, were randomized at a 1:1 ratio to receive 20 mg of teneligliptin (n=35) or placebo (n=30) for 12 weeks. The main endpoints were the changes in HbA1c levels from baseline to week 12, CGM metrics-derived time in range, and glycemic variability.
Results
After 12 weeks, a significant reduction (by 0.84%) in HbA1c levels was observed in the teneligliptin group compared to that in the placebo group (by 0.08%), with a between-group least squares mean difference of –0.76% (95% confidence interval [CI], –1.08 to –0.44). The coefficient of variation, standard deviation, and mean amplitude of glycemic excursion significantly decreased in participants treated with teneligliptin as compared to those in the placebo group. Teneligliptin treatment significantly decreased the time spent above 180 or 250 mg/dL, respectively, without increasing the time spent below 70 mg/dL. The mean percentage of time for which glucose levels remained in the 70 to 180 mg/dL time in range (TIR70–180) at week 12 was 82.0%±16.0% in the teneligliptin group, and placebo-adjusted change in TIR70–180 from baseline was 13.3% (95% CI, 6.0 to 20.6).
Conclusion
Teneligliptin effectively reduced HbA1c levels, time spent above the target range, and glycemic variability, without increasing hypoglycemia in our study population.

Citations

Citations to this article as recorded by  
  • Comparison of teneligliptin and other gliptin-based regimens in addressing insulin resistance and glycemic control in type 2 diabetic patients: a cross-sectional study
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  • A prospective multicentre open label study to assess effect of Teneligliptin on glycemic control through parameters of time in range (TIR) Metric using continuous glucose monitoring (TOP-TIR study)
    Banshi Saboo, Suhas Erande, A.G. Unnikrishnan
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  • Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes
    Min Jeong Park, Kyung Mook Choi
    Diabetes & Metabolism Journal.2022; 46(1): 49.     CrossRef
Drug/Regimen
Article image
Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study
Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Kim, Hye Soon Kim, Il Seong Nam-Goong, Eun Sook Kim, Jin Ook Chung, Dong-Hyeok Cho, Chang Won Lee, Young Il Kim, Dong Jin Chung, Kyu Chang Won, In Joo Kim, Tae Sun Park, Duk Kyu Kim, Hosang Shon
Diabetes Metab J. 2021;45(5):675-683.   Published online August 12, 2020
DOI: https://doi.org/10.4093/dmj.2020.0107
  • 36,940 View
  • 391 Download
  • 10 Web of Science
  • 7 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Methods

From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.

Results

In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy.

Conclusion

This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Citations

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    Diabetes, Obesity and Metabolism.2021; 23(2): 609.     CrossRef
Review
Complications
Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment
Sunghwan Suh, Kwang-Won Kim
Diabetes Metab J. 2019;43(6):733-743.   Published online December 23, 2019
DOI: https://doi.org/10.4093/dmj.2019.0177
  • 10,247 View
  • 285 Download
  • 103 Web of Science
  • 111 Crossref
AbstractAbstract PDFPubReader   

Cancer incidence appears to be increased in both type 1 and type 2 diabetes mellitus (DM). DM represents a risk factor for cancer, particularly hepatocellular, hepatobiliary, pancreas, breast, ovarian, endometrial, and gastrointestinal cancers. In addition, there is evidence showing that DM is associated with increased cancer mortality. Common risk factors such as age, obesity, physical inactivity and smoking may contribute to increased cancer risk in patients with DM. Although the mechanistic process that may link diabetes to cancer is not completely understood yet, biological mechanisms linking DM and cancer are hyperglycemia, hyperinsulinemia, increased bioactivity of insulin-like growth factor 1, oxidative stress, dysregulations of sex hormones, and chronic inflammation. However, cancer screening rate is significantly lower in people with DM than that in people without diabetes. Evidence from previous studies suggests that some medications used to treat DM are associated with either increased or reduced risk of cancer. However, there is no strong evidence supporting the association between the use of anti-hyperglycemic medication and specific cancer. In conclusion, all patients with DM should be undergo recommended age- and sex appropriate cancer screenings to promote primary prevention and early detection. Furthermore, cancer should be screened in routine diabetes assessment.

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Response
Response: Increased Risk of Hospitalization for Heart Failure with Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health Insurance Claims Database (Diabetes Metab J 2015;39:247-52)
Sunghwan Suh, Gi Hyeon Seo, Chang Hee Jung, Mee-Kyoung Kim, Sang-Man Jin, You-Cheol Hwang, Byung-Wan Lee, Jae Hyeon Kim
Diabetes Metab J. 2015;39(4):350-351.   Published online August 17, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.4.350
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Review
Glycemic Variability: How Do We Measure It and Why Is It Important?
Sunghwan Suh, Jae Hyeon Kim
Diabetes Metab J. 2015;39(4):273-282.   Published online August 17, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.4.273
  • 22,712 View
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  • 263 Web of Science
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AbstractAbstract PDFPubReader   

Chronic hyperglycemia is the primary risk factor for the development of complications in diabetes mellitus (DM); however, it is believed that frequent or large glucose fluctuations may independently contribute to diabetes-related complications. Postprandial spikes in blood glucose, as well as hypoglycemic events, are blamed for increased cardiovascular events in DM. Glycemic variability (GV) includes both of these events; hence, minimizing GV can prevent future cardiovascular events. Correcting GV emerges as a target to be pursued in clinical practice to safely reduce the mean blood glucose and to determine its direct effects on vascular complications in diabetes. Modern diabetes management modalities, including glucagon-related peptide-1-based therapy, newer insulins, modern insulin pumps and bariatric surgery, significantly reduce GV. However, defining GV remains a challenge primarily due to the difficulty of measuring it and the lack of consensus regarding the optimal approach for its management. The purpose of this manuscript was not only to review the most recent evidence on GV but also to help readers better understand the available measurement options and how the various definitions relate differently to the development of diabetic complications.

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Original Articles
Increased Risk of Hospitalization for Heart Failure with Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health Insurance Claims Database
Sunghwan Suh, Gi Hyeon Seo, Chang Hee Jung, Mee-Kyoung Kim, Sang-Man Jin, You-Cheol Hwang, Byung-Wan Lee, Jae Hyeon Kim
Diabetes Metab J. 2015;39(3):247-252.   Published online April 22, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.3.247
  • 4,619 View
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AbstractAbstract PDFPubReader   
Background

We assessed the association of dipeptidyl peptidase 4 inhibitors (DPP4i) with hospitalization for heart failure (HF) using the Korean Health Insurance claims database.

Methods

We collected data on newly prescribed sitagliptin, vildagliptin, and pioglitazone between January 1, 2009 and December 31, 2012 (mean follow-up of 336.8 days) to 935,519 patients with diabetes (518,614 males and 416,905 females) aged 40 to 79 years (mean age of 59.4 years).

Results

During the study, 998 patients were hospitalized for primary HF (115.7 per 100,000 patient-years). The incidence rate of hospitalization for HF was 117.7 per 100,000 per patient-years among patients on pioglitazone, 105.7 for sitagliptin, and 135.8 for vildagliptin. The hospitalization rate for HF was greatest in the first 30 days after starting the medication, which corresponded to a significantly higher incidence at days 0 to 30 compared with days 31 to 360 for all three drugs. The hazard ratios were 1.85 (pioglitazone), 2.00 (sitagliptin), and 1.79 (vildagliptin). The incidence of hospitalization for HF did not differ between the drugs for any time period.

Conclusion

This study showed an increase in hospitalization for HF in the initial 30 days of the DPP4i and pioglitazone compared with the subsequent follow-up period. However, the differences between the drugs were not significant.

Citations

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A Randomized Controlled Trial of an Internet-Based Mentoring Program for Type 1 Diabetes Patients with Inadequate Glycemic Control
Sunghwan Suh, Cheol Jean, Mihyun Koo, Sun Young Lee, Min Ja Cho, Kang-Hee Sim, Sang-Man Jin, Ji Cheol Bae, Jae Hyeon Kim
Diabetes Metab J. 2014;38(2):134-142.   Published online April 18, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.2.134
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AbstractAbstract PDFPubReader   
Background

To determine whether an internet-based mentoring program can improve glycemic control in subjects with type 1 diabetes mellitus (T1DM).

Methods

Subjects with T1DM on intensive insulin therapy and with hemoglobin A1c (HbA1c) ≥8.0% were randomized to mentored (glucometer transmission with feedback from mentors) or control (glucometer transmission without feedback) groups and were examined for 12 weeks. Five mentors were interviewed and selected, of which two were T1DM patients themselves and three were parents with at least one child diagnosed with T1DM since more than 5 years ago.

Results

A total of 57 T1DM adult subjects with a mean duration after being diagnosed with diabetes of 7.4 years were recruited from Samsung Medical Center. Unfortunately, the mentored group failed to show significant improvements in HbA1c levels or other outcomes, including the quality of life, after completion of the study. However, the mentored group monitored their blood glucose (1.41 vs. 0.30) and logged into our website (http://ubisens.co.kr/) more frequently (20.59 times vs. 5.07 times) than the control group.

Conclusion

A 12-week internet-based mentoring program for T1DM patients with inadequate glycemic control did not prove to be superior to the usual follow-up. However, the noted increase in the subjects' frequency of blood glucose monitoring may lead to clinical benefits.

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Education as Prescription for Patients with Type 2 Diabetes Mellitus: Compliance and Efficacy in Clinical Practice
Mi Yeon Kim, Sunghwan Suh, Sang-Man Jin, Se Won Kim, Ji Cheol Bae, Kyu Yeon Hur, Sung Hye Kim, Mi Yong Rha, Young Yun Cho, Myung-Shik Lee, Moon Kyu Lee, Kwang-Won Kim, Jae Hyeon Kim
Diabetes Metab J. 2012;36(6):452-459.   Published online December 12, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.6.452
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AbstractAbstract PDFPubReader   
Background

Diabetes self-management education has an important role in diabetes management. The efficacy of education has been proven in several randomized trials. However, the status of diabetes education programs in real Korean clinical practice has not yet been evaluated in terms of patient compliance with the education prescription.

Methods

We retrospectively analyzed clinical and laboratory data from all patients who were ordered to undergo diabetes education during 2009 at Samsung Medical Center, Seoul, Korea (n=2,291). After excluding ineligible subjects, 588 patients were included in the analysis.

Results

Among the 588 patients, 433 received education. The overall compliance rate was 73.6%, which was significantly higher in the subjects with a short duration or living in a rural area compared to those with a long duration (85.0% vs. 65.1%, respectively; P<0.001) or living in an urban area (78.2% vs. 70.4%, respectively; P=0.037). The hemoglobin A1c decreased greater in the compliant group (from 7.84±1.54 at baseline to 6.79±1.06 at 3 months and 6.97±1.20 at 12 months after prescription in the compliant group vs. from 7.74±1.25 to 7.14±1.02 and 7.24±1.24 in the non-compliant group; P=0.001). The decrease in hemoglobin A1c was greater in the subjects with a short duration (P=0.032).

Conclusion

In our study a large percent of patients refuse to get education despite having a prescription from their physician. This refusal rate was higher in the patients with long-standing diabetes or in urban residence. Furthermore, education was more effective in patients with a short duration of diabetes in clinical practice.

Citations

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  • Clinical Effects of a Home Care Pilot Program for Patients with Type 1 Diabetes Mellitus: A Retrospective Cohort Study
    Sejeong Lee, KyungYi Kim, Ji Eun Kim, Yura Hyun, Minyoung Lee, Myung-Il Hahm, Sang Gyu Lee, Eun Seok Kang
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    Jin Hee Jung, Jung Hwa Lee, Hyang Mi Jang, Young Na, Hee Sun Choi, Yeon Hee Lee, Yang Gyo Kang, Na Rae Kim, Jeong Rim Lee, Bok Rye Song, Kang Hee Sim
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Cardio-Metabolic Features of Type 2 Diabetes Subjects Discordant in the Diagnosis of Metabolic Syndrome
Sa Rah Lee, Ying Han, Ja Won Kim, Ja Young Park, Ji Min Kim, Sunghwan Suh, Mi-Kyoung Park, Hye-Jeong Lee, Duk Kyu Kim
Diabetes Metab J. 2012;36(5):357-363.   Published online October 18, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.5.357
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AbstractAbstract PDFPubReader   
Background

The aim of this study is to investigate the cardio-metabolic parameters and surrogate markers of insulin resistance in a discordant group of type 2 diabetes (T2DM) subjects who satisfy the Adults Treatment Panel (ATP) III criteria, but not the International Diabetes Federation (IDF) criteria, for metabolic syndrome (MetS).

Methods

We assessed the prevalence of MetS in T2DM subjects (n=167) who were selected from subjects registered at the diabetes center of Dong-A University Medical Center. We used the ATP III criteria and the IDF criteria for the diagnosis of MetS and sorted the subjects into 2 MetS groups: one group diagnosed per ATP III criteria (MetSa) and one diagnosed per IDF criteria (MetSi). We then compared the clinical characteristics, metabolic parameters (homeostasis model assessment of insulin resistance, aspartate aminotransferase, alanine aminotransferase, and uric acid values) and co-morbidities (prevalence of microalbuminuria, fatty liver, and cardiovascular disease) between the MetSa, MetSi, and discordant MetS groups.

Results

The prevalence of MetS in the MetSa group (73.6%) was higher than in the MetSi group (62.2%). The MetS prevalence in the discordant group was 11.4%. The discordant group showed no significant differences in clinical characteristics (except waist circumference and body mass index), metabolic parameters, or prevalence of co-morbidities, as compared with subjects with MetS by both criteria.

Conclusion

In this study, cardio-metabolic features of the subjects diagnosed with MetS using ATP III criteria, but not IDF criteria, are not significantly different from those of subjects diagnosed with MetS using both criteria.

Citations

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    Ping Liu, Shujian Sui, Dongling Xu, Xiaowei Xing, Caixia Liu
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Smaller Mean LDL Particle Size and Higher Proportion of Small Dense LDL in Korean Type 2 Diabetic Patients
Sunghwan Suh, Hyung-Doo Park, Se Won Kim, Ji Cheol Bae, Alice Hyun-Kyung Tan, Hye Soo Chung, Kyu Yeon Hur, Jae Hyeon Kim, Kwang-Won Kim, Moon-Kyu Lee
Diabetes Metab J. 2011;35(5):536-542.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.536
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AbstractAbstract PDFPubReader   
Background

Small dense low density lipoprotein (sdLDL) has recently emerged as an important risk factor of coronary heart disease.

Methods

The mean LDL particle size was measured in 203 patients with type 2 diabetes mellitus (T2DM) and 212 matched subjects without diabetes using polyacrylamide tube gel electrophoresis. Major vascular complications were defined as stroke, angiographically-documented coronary artery disease or a myocardial infarction. Peripheral vascular stenosis, carotid artery stenosis (≥50% in diameter) or carotid artery plaque were considered minor vascular complications. Overall vascular complications included both major and minor vascular complications.

Results

Diabetic patients had significantly smaller mean-LDL particle size (26.32 nm vs. 26.49 nm) and a higher percentage of sdLDL to total LDL compared to those of subjects without diabetes (21.39% vs. 6.34%). The independent predictors of sdLDL in this study were serum triglyceride level and body mass index (odds ratio [OR], 1.020 with P<0.001 and OR 1.152 with P<0.027, respectively). However, no significant correlations were found between sdLDL and major vascular complications (P=0.342), minor vascular complications (P=0.573) or overall vascular complications (P=0.262) in diabetic subjects.

Conclusion

Diabetic patients had a smaller mean-LDL particle size and higher proportion of sdLDL compared to those of subjects without diabetes. Obese diabetic patients with hypertriglyceridemia have an increased risk for atherogenic small dense LDL. However, we could not verify an association between LDL particle size and vascular complications in this study.

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Effects of Resistance Training and Aerobic Exercise on Insulin Sensitivity in Overweight Korean Adolescents: A Controlled Randomized Trial
Sunghwan Suh, In-Kyong Jeong, Mi Yeon Kim, Yeon Soo Kim, Sue Shin, Sun Sin Kim, Jae Hyeon Kim
Diabetes Metab J. 2011;35(4):418-426.   Published online August 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.4.418
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AbstractAbstract PDFPubReader   
Background

Data on the impact of resistance training on insulin resistance in overweight or obese children are inconclusive.

Methods

Thirty overweight South Korean adolescents (mean age of 13.10 years) were divided by sex, and then randomly assigned to one of three treatment groups, which were the diet only (DO), diet with aerobic exercise (AE), or diet with resistance training (RT) group. Physiologic and metabolic parameters were assessed at baseline and after 12 weeks of exercise training and diet modification.

Results

Both exercise groups (aerobic and resistance) showed significant improvements in their insulin area under the curve and insulin sensitivity index values when compared to their baseline values while the DO group showed no significant changes in these variables. Age-, sex-, and body mass index (BMI)-adjusted intergroup comparison analyses showed a marked reduction in BMI and a significant reduction in muscle mass in the AE group when compared to the RT group and the DO group, respectively.

Conclusion

A 12-week exercise training program of either resistance or aerobic activity improved insulin sensitivity in overweight adolescents, although it failed to show superiority over a DO program. Aerobic exercise decreased both body weight and BMI, and it was noted that this group also had a significant reduction in muscle mass when compared to the DO group.

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Review
Diabetes and Cancer: Is Diabetes Causally Related to Cancer?
Sunghwan Suh, Kwang-Won Kim
Diabetes Metab J. 2011;35(3):193-198.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.193
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AbstractAbstract PDFPubReader   

Diabetes mellitus is a serious and growing health problem worldwide and is associated with severe acute and chronic complications. Moreover, epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer. Several studies indicate an association between diabetes and the risk of liver, pancreas, endometrium, colon/rectum, breast, and bladder cancer. Mortality is also moderately increased in subjects with diabetes. Common risk factors such as age, obesity, physical inactivity and smoking may contribute to increased cancer risk in diabetic patients. Hyperinsulinemia most likely favors cancer in diabetic patients as insulin is a growth factor with pre-eminent metabolic as well as mitogenic effects, and its action in malignant cells is favored by mechanisms acting at both the receptor and post-receptor level. The effect of diabetes treatment drugs, aside from metformin, on cancer is not conclusive. In order to fight the perfect storm of diabetes and cancer, strategies to promote primary prevention and early detection of these conditions are urgently needed.

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Diabetes Metab J : Diabetes & Metabolism Journal
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