7 Complications of Diabetes

Suggested citation: Endocrine Society. Endocrine Facts and Figures: Diabetes. First Edition. 2015.

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The acute complications of diabetes include diabetic ketoacidosis, and severe glycemic crisis (hypoglycemia and hyperglycemia). The chronic complications of diabetes are divided into microvascular complications, which occur exclusively in individuals with diabetes and include neuropathy, retinopathy, and nephropathy; and macrovascular complications which occur more commonly in individuals with diabetes and include atherosclerotic vascular disease, stroke, and lower-limb amputations adverse cardiovascular outcomes.

An evaluation of data from NHANES and the Behavioral Risk Factor Surveillance System (BRFSS) reported that most diagnosed persons with diabetes undergo annual examinations to check for common complications of diabetes. For example, data from 1999–2010 indicate that 71.4% of persons with diagnosed diabetes undergo an annual foot exam.59 In addition, according to the National Hospital Discharge Survey (NHDS), diabetes-related lower extremity amputation rates decreased by 0.8 per 1,000 per year nationwide between 1996 and 2002.92 Table 31 presents data on changes in the prevalence of some macrovascular complications of diabetes between 1990 and 2010. The remainder of this section will focus on the microvascular complications of diabetes.

Table 31. Prevalence of macrovascular complications of diabetes among United States adults, 1990-2010.
Complication Data Source Population Prevalence
      1990 2010
Acute myocardial infarction National Hospital Discharge Survey US adults, age 20+ years 1.41% 0.46%
Stroke National Hospital Discharge Survey US adults, age 20+ years 1.12% 0.53%
Lower-limb amputation National Hospital Discharge Survey US adults, age 20+ years 0.58% 0.28%

Source: Gregg et al. 201414

7.1         DIABETIC NEUROPATHY

Diabetic neuropathy is a group of nerve disorders caused by diabetes.93,94 These include peripheral neuropathy, autonomic neuropathy, proximal neuropathy, and focal neuropathy. The risk of developing diabetic neuropathy increases with age, longer duration of diabetes, and poorer control of blood glucose.

7.1.1     PREVALENCE AND INCIDENCE

The prevalence of diabetic peripheral neuropathy (DPN) has been extensively studied. However, data are incomplete for the prevalence of other types of neuropathies. The prevalence of diabetic neuropathy is higher among older diabetes patients and may vary depending on the type of diabetes (Table 32).

Table 32. Prevalence of diabetic peripheral neuropathy.
Data Source Population Prevalence Reference
1999-2002 NHANES Persons diagnosed with diabetes, age 40+ years 21.2% Cheng et al. 20068
1999-2002 NHANES Persons diagnosed with diabetes, age 40+ years 21.5% Koopman et al. 20069
1999-2000 NHANES Persons diagnosed with diabetes, age 40+ years 28.5% Gregg et al. 200495
SEARCH for Diabetes in Youth Type 2 diabetes patients, age <20 years 25.7% Jaiswal et al. 201396
SEARCH for Diabetes in Youth Type 1 diabetes patients, age <20 years 8.2% Jaiswal et al. 201396

Abbreviation: NHANES, National Health and Nutrition Examination Survey

7.1.2     DEMOGRAPHIC DIFFERENCES

No differences have been reported in risk of neuropathy among whites, blacks, and Hispanics in the US. 97-99 There are no known sex differences in the risk of developing diabetic neuropathy.

7.1.3     LIFE EXPECTANCY AND MORTALITY

A meta-analysis of 15 studies100, published between 1966-2001, revealed an association between cardiovascular autonomic neuropathy and increased relative risk for mortality (1.20) in people with diabetes, though not as strong as previously reported by others.

7.1.4     KEY TRENDS AND HEALTH OUTCOMES

Diabetic peripheral neuropathy (DPN) is an underdiagnosed condition. In one cross-sectional study of patients with type 2 diabetes from rural Arkansas, 9.6% had a diabetic peripheral neuropathy diagnosis and 43% reported symptoms of peripheral neuropathy; 79% of those with symptoms had not been diagnosed with DPN.101

The drugs duloxetine and pregabalin are approved by the Food and Drug Administration for the treatment of diabetic neuropathic pain. However, a study of diagnosed DPN patients seeing community-based practitioners throughout the US indicated that NSAIDs were the class most commonly prescribed to treat neuropathy patients. The study identified treatment practices and approaches, summarized in Table 33.102

Table 33. DPN patients: treatment adherence and opinions.
Frequency of professional consultations for DPN
       2 or more in preceding 3 months 59.6%
       4 or more in preceding 3 months 41.2%
Prescription medication behavior and attitudes
       Mean prescription medication types in preceding week 3.8
       Used at least 1 medication 79.2%
       Used at least 2 medications 52.2%
       Used prescription NSAIDs 46.7%
       Satisfied with medications 22.4%
       Considered medications effective 23.1%
Over-the-counter (OTC) medication: behavior and attitudes
Mean OTC medication types in preceding week 2.1
Used acetaminophen 36.1%
Satisfied with medications 7.8%
Considered medications effective 6.7%

Source: Gore et al. 2006102

7.2         DIABETIC RETINOPATHY

Diabetic retinopathy is a condition in which high blood glucose causes damage to the blood vessels in the retina.103,104

In nonproliferative retinopathy, blood vessels swell or become blocked. In proliferative retinopathy, damaged blood vessels deprive the retina of oxygen, causing new vessels to grow along the retina and on the surface of the gel, or vitreous, inside of the eye. 103,104

7.2.1     PREVALENCE AND INCIDENCE

Diabetic retinopathy occurs in both type 1 and type 2 diabetes; the likelihood of developing the condition increases with duration of disease and is higher in people with uncontrolled blood glucose levels (Table 34).

Table 34. Prevalence of Diabetic Retinopathy.
Condition Data Source Population Prevalence References
Diabetic retinopathy 2005-2008 NHIS Patients with diabetes, age 40+ years 28.5% Zhang et al. 201010
Any retinopathy MESA Patients with diabetes, age 45-85 years 33.2% Wong et al. 200611
Macular edema MESA Patients with diabetes, age 45-85 years 9.0% Wong et al. 200611
Vision impairment 2010 NHIS Patients with self-reported diabetes 16.7% Centers for Disease Control and Prevention. 201121
Vision-threatening diabetic retinopathy 2005-2008 NHIS Patients with diabetes, age 40+ years 4.4% Zhang et al. 201010

Abbreviations: MESA, Multi-Ethnic Study of Atherosclerosis; NHIS, National Health Interview Survey

The 2005-2008 NHIS data indicated that both retinopathy and vision-threatening retinopathy were higher among males than females10 (Table 35).

Table 35. Prevalence and severity of diabetic retinopathy by sex.
Sex Diabetic Retinopathy (prevalence among patients with diabetes) Vision-Threatening Diabetic Retinopathy (prevalence among patients with diabetes)
Males 31.6% 25.7%
Females 4.2% 4.7%

Source: Zhang et al. 201010

7.2.2     DEMOGRAPHIC DIFFERENCES

Based on NHIS data from 2005 to 2008, the crude prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy in patients over 40 years of age were highest among non-Hispanic blacks10 (Table 36).

Table 36. Prevalence of diabetic retinopathy by race/ethnicity.
Race/ethnicity Diabetic Retinopathy (prevalence among patients with diabetes) Vision-Threatening Diabetic Retinopathy (prevalence among patients with diabetes)
Non-Hispanic Black 38.8% 9.3%
Mexican American 34.0% 7.3%
Non-Hispanic White 2.4% 3.2%

Source: Zhang et al. 201010

7.2.3     LIFE EXPECTANCY AND MORTALITY

A long-term epidemiological study in a Wisconsin population of type 1 diabetes patients revealed that diabetic retinopathy was associated with cardiovascular end points such as angina, stroke, and myocardial infarction.105 The severity of retinopathy was associated with mortality from heart disease, which was consistent across all age groups examined. Sex differences in the relationship between retinopathy and cardiovascular outcomes were not apparent in this study. The hazard ratio for mortality involving heart disease, including diabetic retinopathy as a variable, was calculated to be 1.3.

7.2.4     KEY TRENDS AND HEALTH OUTCOMES

Most patients with diagnosed diabetes undergo annual examinations to check for common complications of diabetes (Table 37).

Table 37. Diagnosis and preventive behaviors related to diabetic retinopathy.
Data Source Population and Behavior Prevalence Reference
1999-2010 NHANES and BRFSS Diagnosed diabetes undergoing annual eye exam 73.4% Ali et al. 201359
1997-2010 NHIS Self-reported diabetes visiting an eye-care provider annually 63% (diabetes + vision impairment)57% (diabetes + no vision impairment Centers for Disease Control and Prevention. 201121

Abbreviations: BRFSS, Behavioral Risk Factor Surveillance System; NHANES, National Health and Nutrition Examination Survey; NHIS, National Health Interview Survey

NHIS data from 1997 to 2010 indicated that whereas self-reported diabetes plus visual impairment in adults increased, the age-adjusted prevalence of visual impairment among diagnosed persons with diabetes decreased 21 (Table 38).

Table 38. Prevalence of visual impairment in self-reported and diagnosed diabetes, US.
1997 2009
Self-reported diabetes 2.7 million 3.9 million
Diagnosed diabetes* 23.7% 16.7%
Note: *, age-adjusted prevalence

Source: Centers for Disease Control and Prevention. 2011 21

The use of macular photocoagulation has reduced the risk of visual impairment by diabetic macular edema. The role of vascular endothelial growth factor (VEGF) in diabetic retinopathy and diabetic macular edema pathogenesis has been demonstrated in recent studies, and the efficacy and safety of intravitral anti-VEGF has recently been demonstrated in clinical trials.106

7.3         DIABETIC NEPHROPATHY

Diabetic nephropathy is a condition in which the kidney becomes damaged, resulting in the scarring of nephrons, the small units that filter the blood and remove waste from the body. 107,108

7.3.1     PREVALENCE AND INCIDENCE

According to NHANES data, diabetic kidney disease affects between 24% and 40% of people with diagnosed diabetes (Table 39).

Table 39.Prevalence of diabetic kidney diseases.
Condition Data Source Population Prevalence Ref.
Any diabetic kidney disease 2005-2008 NHANES Patients with diagnosed diabetes, age 20+ years 34.5% De Boer et al. 201112
Albuminuria 2005-2008 NHANES Patients with diagnosed diabetes, age 20+ years 23.7% De Boer et al. 201312
Nephropathy 1999-2002 NHANES Patients with diagnosed diabetes, age 40+ years 26.5% Koopman et al. 20069
Chronic kidney disease 1999-2006 NHANES Patients with diagnosed diabetes, age 20+ years 39.6% Plantinga et al. 201013
1999-2006 NHANES Persons with undiagnosed diabetes, age 20+ years 41.7% Plantinga et al. 201013
1999-2006 NHANES Patients with prediabetes, age 20+ years 17.7% Plantinga et al. 201013
Renal disease 1997-1999 Veterans Health Administration data VA patients with diagnosed diabetes 10.4% Young et al. 2003109

Abbreviation: NHANES, National Health and Nutrition Examination Survey

With adjustments for demographic factors, evaluation of three installments of NHANES data (1988–1994, 1999–2004 and 2005–2008) indicated no change in the prevalence of any diabetic kidney disease or albuminuria between 1988 and 2008.12

7.3.2     DEMOGRAPHIC DIFFERENCES

A retrospective study of over 15,000 health records of diabetes patients with no prior history of kidney disease found differing rates of diabetic kidney disease (DKD). Racial/ethnic minorities had higher rates of proteinuric DKD than non-Hispanic whites and lower rates of nonproteinuric DKD. Chinese, Filipino, Hispanic, and non-Hispanic black females exhibited significantly higher odds of proteinuric DKD than non-Hispanic whites. Conversely, Chinese, Hispanic, and non-Hispanic black females and Hispanic males had significantly lower odds of nonproteinuric DKD than NHWs 110 (Table 40).

Table 40. Rates of diabetic kidney disease by race/ethnicity.
Race/ethnicity Proteinuric DKD Nonproteinuric DKD
Non-Hispanic white 24.8% 11.7%
Asian Indian 24.8% 9.7%
Chinese 27.6% 6.3%
Filipino 37.9% 9.8%
Hispanic 32.5% 7.6%
Non-Hispanic black 35.3% 6.9%

Source: Bhalla et al. 2013110

7.3.3     LIFE EXPECTANCY AND MORTALITY

For patients with type 2 diabetes and nephropathy, the Charlson comorbidity index (CCI), along with hemoglobin and serum albumin, is an effective predictor of mortality. 111 533 Chinese patients with type 2 DN with comorbidity CCI score >1, 44.7% (238/533) died. Mortality increased with CCI scores: 21.0% (50/238) patients with CCI scores of 1-2, 56.7% (135/238) patients with CCI scores of 3-4, and 22.3% (53/238) patients with CCI scores >/=5.112

7.3.4     KEY TRENDS AND HEALTH OUTCOMES

In 2011, according to the United States Renal Data System, diabetes was listed as the primary cause of kidney failure in 44% of all new cases.113 Table 41 presents data on differences in mortality rate among Medicare patients based on different disease profiles.

Table 41. Mortality among Medicare patients age 66 years and older by disease profile.
Disease profile Mortality
No diabetes, chronic kidney disease, or cardiovascular disease 40 per 1,000 patient-years
Diabetes 50 per 1,000 patient-years
Diabetes, chronic kidney disease, cardiovascular disease 100 per 1,000 patient-years

Source: National Institute of Diabetes and Digestive and Kidney Diseases. 2013113

According to 1999-2004 data from NHANES, awareness of chronic kidney disease among adult persons with diabetes with stage 3 chronic kidney disease (CKD) rose from 12.2% in 1999-2000 to 19.1% in 2003-2004.13

Increased systolic blood pressure variability between outpatient events is associated with increased incidence of cardiovascular end points. A post-hoc analysis of two observational trials showed that greater visit-to-visit variability of systolic blood pressure was associated independently with more rapid doubling of serum creatinine and end-stage renal disease, but not with time to cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, or revascularization.111

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