Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of DAN has not been fully appreciated. The reported prevalence of DAN varies widely depending on the cohort studied and the methods of assessment. In randomly selected cohorts of asymptomatic individuals with diabetes, 20% had abnormal cardiovascular autonomic function. DAN frequently coexists with other peripheral neuropathies and other diabetic complications, but DAN may be isolated, frequently preceding the detection of other complications. Major clinical manifestations of DAN include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastro- paresis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, "brit- tle diabetes," and hypoglycemic autonomic failure. DAN may affect many organ systems throughout the body (e.g., gastrointestinal (GI), genitourinary, and cardiovascular). GI distur- bances (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, and fecal inconti- nence) are common, and any section of the GI tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control. Upper-GI symptoms should lead to con- sideration of all possible causes, including autonomic dysfunction. Whereas a radiographic gastric emptying study can definitively establish the diagnosis of gastroparesis, a reasonable approach is to exclude autonomic dysfunction and other known causes of these upper-GI symptoms. Constipation is the most common lower-GI symptom but can alternate with episodes of diarrhea. Diagnostic approaches should rule out autonomic dysfunction and the well-known causes such as neoplasia. Occasionally, anorectal manometry and other specialized tests typically performed by the gastroenterologist may be helpful. DAN is also associated with genitourinary tract disturbances including bladder and/or sexual dysfunction. Evaluation of bladder dysfunc- tion should be performed for individuals with diabetes who have recurrent urinary tract infec- tions, pyelonephritis, incontinence, or a palpable bladder. Specialized assessment of bladder dysfunction will typically be performed by a urologist. In men, DAN may cause loss of penile erection and/or retrograde ejaculation. A complete workup for erectile dysfunction in men should include history (medical and sexual); psychological evaluation; hormone levels; mea- surement of nocturnal penile tumescence; tests to assess penile, pelvic, and spinal nerve func- tion; cardiovascular autonomic function tests; and measurement of penile and brachial blood pressure. Neurovascular dysfunction resulting from DAN contributes to a wide spectrum of clinical disorders including erectile dysfunction, loss of skin integrity, and abnormal vascular reflexes. Disruption of microvascular skin blood flow and sudomotor function may be among the earliest manifestations of DAN and lead to dry skin, loss of sweating, and the development of fissures and cracks that allow microorganisms to enter. These changes ultimately contribute to the development of ulcers, gangrene, and limb loss. Various aspects of neurovascular function can be evaluated with specialized tests, but generally these have not been well standardized and have limited clinical utility. Cardiovascular autonomic neuropathy (CAN) is the most studied and clinically important form of DAN. Meta-analyses of published data demonstrate that reduced cardiovascular autonomic function as measured by heart rate variability (HRV) is strongly (i.e., relative risk is doubled) associated with an in- creased risk of silent myocardial ischemia and mortality. The determination of the presence of CAN is usually based on a battery of auto- nomic function tests rather than just on one test. Proceedings from a consensus conference in 1992 recommended that three tests (R-R variation, Valsalva maneuver, and postural blood pressure testing) be used for longitudi- nal testing of the cardiovascular autonomic system. Other forms of autonomic neuropathy can be evaluated with specialized tests, but these are less standardized and less available than commonly used tests of cardiovascular autonomic function, which quantify loss of HRV. Interpretability of serial HRV testing re- quires accurate, precise, and reproducible procedures that use established physiological maneuvers. The battery of three recom- mended tests for assessing CAN is readily per- formed in the average clinic, hospital, or diagnostic center with the use of available technology. Measurement of HRV at the time of diagnosis of type 2 diabetes and within 5 years after diagnosis of type 1 diabetes (unless an individual has symptoms suggestive of au- tonomic dysfunction earlier) serves to estab- lish a baseline, with which 1-year interval tests can be compared. Regular HRV testing pro- vides early detection and thereby promotes timely diagnostic and therapeutic interven- tions. HRV testing may also facilitate differen- tial diagnosis and the attribution of symptoms (e.g., erectile dysfunction, dyspepsia, and diz- ziness) to autonomic dysfunction. Finally, knowledge of early autonomic dysfunction can encourage patient and physician to im- prove metabolic control and to use therapies such as ACE inhibitors and -blockers, proven to be effective for patients with CAN. Diabetes Care 26:1553-1579, 2003

/pdf/diabetic-autonomic-neuropathy-4kabtayo3d.pdf

Diabetic Autonomic Neuropathy

Although physical activity (PA) is a key element in the prevention and management of type 2 diabetes, many with this chronic disease do not become or remain regularly active. High-quality studies establishing the importance of exercise and fitness in diabetes were lacking until recently, but it is now well established that participation in regular PA improves blood glucose control and can prevent or delay type 2 diabetes, along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life. Structured interventions combining PA and modest weight loss have been shown to lower type 2 diabetes risk by up to 58% in high-risk populations. Most benefits of PA on diabetes management are realized through acute and chronic improvements in insulin action, accomplished with both aerobic and resistance training. The benefits of physical training are discussed, along with recommendations for varying activities, PA-associated blood glucose management, diabetes prevention, gestational diabetes mellitus, and safe and effective practices for PA with diabetes-related complications.

https://care.diabetesjournals.org/content/diacare/33/12/2692.full.pdf

Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement.

One of the most overlooked of all serious complications of diabetes is cardiovascular autonomic neuropathy (CAN),1–3 which encompasses damage to the autonomic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics.4

The present report discusses the clinical manifestations (eg, resting tachycardia, orthostasis, exercise intolerance, intraoperative cardiovascular liability, silent myocardial infarction [MI], and increased risk of mortality) in the presence of CAN. It also demonstrates that autonomic dysfunction can affect daily activities of individuals with diabetes and may invoke potentially life-threatening outcomes. Advances in technology, built on decades of research and clinical testing, now make it possible to objectively identify early stages of CAN with the use of careful measurement of autonomic function and to provide therapeutic choices that are based on symptom control and that might abrogate the underlying disorder.

Little information exists as to frequency of CAN in representative diabetic populations. This is further complicated by the differences in the methodology used and the lack of standardization. Fifteen studies using different end points report prevalence rates of 1% to 90%.1 The heterogenous methodology makes it difficult to compare epidemiology across different studies. CAN may be present at diagnosis, and prevalence increases with age, duration of diabetes, and poor glycemic control. CAN also cosegregates with distal symmetric polyneuropathy, microangiopathy, and macroangiopathy. Age, diabetes, obesity, and smoking are risk factors for reduced heart rate variability (HRV)5 in type 2 diabetes. Thus, there may be selectivity and sex-related differences among the various cardiovascular risk factors as to their influence on autonomic dysfunction.6 HbA1c, hypertension, distal symmetrical polyneuropathy, retinopathy, and exposure to hyperglycemia were shown to be risk factors for developing CAN in type 1 diabetes.7

### Resting Tachycardia

Whereas abnormalities in HRV are early findings of CAN, resting tachycardia …

Diabetic Cardiovascular Autonomic Neuropathy

Although physical activity (PA) is a key element in the prevention and management of type 2 diabetes mellitus (T2DM), many with this chronic disease do not become or remain regularly active. High-quality studies establishing the importance of exercise and fitness in diabetes were lacking until recently, but it is now well established that participation in regular PA improves blood glucose control and can prevent or delay T2DM, along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life. Structured interventions combining PA and modest weight loss have been shown to lower T2DM risk by up to 58% in high-risk populations. Most benefits of PA on diabetes management are realized through acute and chronic improvements in insulin action, accomplished with both aerobic and resistance training. The benefits of physical training are discussed, along with recommendations for varying activities, PA-associated blood glucose management, diabetes prevention, gestational diabetes, and safe and effective practices for PA with diabetes-related complications.

/pdf/exercise-and-type-2-diabetes-american-college-of-sports-1tlqyozkqx.pdf

Exercise and type 2 diabetes: American College of Sports Medicine and the American Diabetes Association: joint position statement. Exercise and type 2 diabetes.

Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 20 randomly selected Type 2 (non-insulin-dependent) diabetic patients receiving oral hypoglycaemic therapy and 20 control subjects In the diabetic patients, the relationships between oesophageal emptying, gastric emptying, gastrointestinal symptoms, autonomic nerve function and glycaemic control were examined The percentage of the solid meal remaining in the stomach at 100 min (p 005) with oesophageal, or gastric emptying The 50% gastric emptying time for the liquid meal was positively related (r=058, p<001) to the plasma glucose concentration at the time of the performance of the gastric emptying test and the lag period, before any solid food emptied from the stomach, was longer (p<005) in subjects with plasma glucose concentrations during the gastric emptying measurement greater than the median, compared to those with glucose concentrations below the median These results indicate that delayed gastric and oesophageal emptying occur frequently in Type 2 diabetes mellitus and that delayed gastric emptying relates, at least in part, to plasma glucose concentrations

/pdf/gastric-and-oesophageal-emptying-in-patients-with-type-2-non-1sjhei2f7u.pdf

Gastric and oesophageal emptying in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Diabetic Autonomic Neuropathy: Present Insights and Future Prospects Autonomic neuropathy is now well recognized as a serious consequence of diabetes mellitus. Although most of the clinical features were described 40 yr ago, the pathophysiological understanding is still far from complete. There are several previous reviews,\" but recent advances make a further consideration of this subject appropriate. The past decade has seen gathering momentum in diabetic autonomic neuropathy research. Simple well-validated and noninvasive tests, particularly tests using cardiovascular reflexes, have now been refined for assessing autonomic nerve damage. Other simple tests involving pupillary, gastrointestinal, genitourinary, and sudomotor function are being developed. The direct recording of impulses conducted by autonomic nerve fibers is now possible with microneurography. With newer concepts of an enlarged autonomic nervous system, neuroendocrine aspects of autonomic dysfunction are increasingly being explored. Although these advances may not seem immediately relevant to the clinician, there have also been parallel developments in the study of the effect on neuropathy of improved glycemic control and newer treatments such as aldose reductase inhibitors and gangliosides. We present the contemporary position of diabetic autonomic neuropathy.

B F Clarke

Papers

Diabetic Autonomic Neuropathy: Present Insights and Future Prospects