This page will try and summarize information on myotonic dystrophy and diabetes.


Pathogenesis of Diabetics in Myotonic Dystrophy.

Myotonic dystrophy (MD) is the most common adult form of muscular dystrophy with an estimated prevalence of 1 in 8000 and is often complicated by diabetes. MD is dominantly inherited and is due to heterozygosity for a tri-nucleotide repeat expansion mutation in a protein kinase gene and it was suggested that this induces derangement of RNA metabolism also able to reduce insulin receptor expression. To test whether the abnormal RNA metabolism or a specific malfunction of protein kinase gene may induce insulin resistance prior to the onset of diabetes, we studied 5 glucose-tolerant MD patients (3F/2M, 41 [+ or -] 8yrs, 59 [+ or -] 7 kg, BMI21 [+ or -] 2 kg/[m.sup.2]) and 5 matched healthy subjects, by means of a) dual x-ray energy absorption b) euglycemic-hyperinsulinemic clamp (1 mU/kg/min) c) primed-continuous infusion of 6,6-[d.sup.2]-glucose and I-[sup.13]C-leucine d) indirect calorimetry. Fasting plasma insulin were similar, but proinsulin concentrations were increased in M!

D patients (p=0.01) and the ratio intact proinsulin/insulin (20 [+ or -] 4% vs 5 [+ or -] 1%; p=0.01) was 4-fold higher in MD. MD showed increased body fat mass (35 [+ or -] 5 vs 26 [+ or -] 2%; p=0.05) but lipid oxidation and FFA concentration in the post absorptive and clamp conditions were comparable between the two groups. Glucose metabolism (oxidative and non-oxidative) during insulin stimulation was comparable to normals (6.9 [+ or -] 1.4 vs 8.2 [+ or -] 1.1 mg/]kg FFM.min]; p=0.49). Leucine flux in the post absorptive condition was slightly increased and its sensitivity to insulin was impaired in MD (suppression =8[+ or -]2 vs 19 [+ or -] 2%; p=0.05); also suppression of plasma glutamine (8 [+ or -] 5%) and phenylalanine (8 [+ or -] 2%) concentrations during the clamp were similar than in normals (33 [+ or -] 7 and 15 [+ or] 3% respectively; p=0.05). In summary, MD showed alterations of protein metabolism in both post absorptive and insulin stimulated conditions resulti!

ng in increased proteolysis and muscle wasting. Insulin dependent glucose metabolism is preserved; therefore insulin resistance for glucose is not a major factor in the pathogenesis of diabetes in MD. On the contrary, abnormal insulin cleavage leading to increased proinsulin levels, probably related to specific protein kinase gene malfunction, represents a marker of secretory dysfunction capable to induce diabetes mellitus.


(*) ADA Professional Section Member. See Duality of Interest Information.

Management of Myotonic dystrophy

This information is from the 11th annual conference of the English Myotonic Dystrophy

“Myotonic Dystrophy Incurable but not Unmanageable”

The incidence of Myotonic Dystrophy is 1 in 8000. Most general practioners have about 2000 patients in their practice. So by simple mathematics only one in four general practioners will see a patient with DM. Most will not know much about it. So it is necessary to have specialized centers for treatment. (Webmaster note: By implication the congenital form is about 1 in 100,000 so that only 1 in 50 pediatricians will have a patient with CMyD in their practice)

Most other muscular dystrophies will only affect the muscles. DM is different in that other systems are affected as well. Another difference is that with most other genetic diseases you either have the gene and the disease or you don’t. DM is a variable genetic disease. It severity differs with the age of onset and the number of repeats. There is not a distinct expression of the disease based on an on or off view. Thus, many medical practioners will have a harder time understanding the disease. The other implication is that you can not generalize the condition of one patient with the disease to another, it is variable

Skeletal Muscle: The skeletal muscle is defined by Myotonia of muscular stiffness, in particular hand stiffness. Also certain other muscles are weak especially facial, scapula and humorous muscles are mostly affected. However, this stiffness is generally not he problems that patients report more, it is the weakness of the hand and other muscles that comes into play. This is more the day to day problems that weaker muscles may cause. Weakness of the grip seems to be the most problematic. A normal male should be able to squeeze about an equivalent of 50Kg. A patient with DM may only be able to squeeze the equivalent of 10-1Kg for example. Also weakness of the ankle muscles causes the characteristic gait of DM. Dr. Jones mentioned that a patient of his was unable to blow into a breathalyzer machine So Dr. Jones felt it was more the practical issues of weakness more than the myotonia that affect DM patients

Smooth Muscles: One of the primary effects of DM on smooth muscle is that swallowing and feeding are much more difficult. What is generally recommended is that food should be cut into small pieces and drink used to wash this down. Care must be taken to avoid aspiration pneumonia, that is food going down into the lungs and causing pneumonia. Dr, Jones mentioned a drug Cysotia?? (Margaret can we get clarification here) or surgery that might be needed to assist. Also a video Fluoroscopy will help diagnosis any feeding problems.

The smooth muscles also affects the bowel and notably irritable bowel syndrome is very common in patients with DM. This is failure of coordination of muscles. Constipation is also a complication because of muscle problems plus immobility of patients not moving. Surgery is not recommend and Dr. Jones has heard reports of patient deaths with surgery. The Uterus is also affected and problems in childbirth may result.

The heart is affected in other dystrophies but in DM it is not the heart muscle itself that is affected. Rather, it is problems with the electrical signals not working properly and the heart either working to fast or too slowly. Atrial fibrillation is when part of the heart is not working efficiently, pumping to fast and not coordinated) and this can cause dizzy spells and blackouts, can be treated. The heart can also pump too slow causing the same symptoms. Heart changes are slow to respond to changes in the body. Dr. Jones recommended an EKG every year to look for problems.

Eyes and Ears: Cataracts can be the first evidence of myotonic dystrophy disease. Generally, if cataracts are seen in patients under 50 DM should be considered. There is nothing special about the mature form of cataracts. However, in the early stages there is a characteristic pattern that can be seen that is unique to DM. A mild degree of deafness is due to DM but not serious.

Brain. On average IQ is a little lower. In the congenital form IQ is reduced and most children will have learning disabilities. The mental problems are pretty static with little change over time.

Excessive Daytime Sleeping: 75% of DM patients have excessive sleepiness. In a survey they conducted 120 responses were received and 40% of patients had a pathological sleeping problem. There is a new drug Modafinil (Brand name Provigil in USA) that might help. Make sure to take it in the morning!

Breathing: The lungs are affected as well as the heart. The anesthesiologist should be informed as well as the surgeon prior to any surgery. Certain precautions must be taken. DM suffers should wear a bracelet as well as cards in case of an accident. The group had a handout on anesthesia that was in some of there earlier newsletters.

Endocrine System: There is reduced fertility in patients with DM. There is also diabetes. Dr. Jones didn’t feel that DM diabetes falls into the classical sense of Diabetes. Feels that all patients with DM have problems with sugar levels. (My note: Might possibly have a different Mechanism of action?). Would be nice to get some more information on this.

Dr. Jones feels that the age of onset is a more potent predictor of outcome versus the number of repeats. There is the anticipation factor where in each generation the outcome becomes progressively worse.

Genetic counseling: Family needs to be screened especially women to prevent them from unknowingly having an infant with CMyD. When an individual is identified strong efforts should be considered to have other family members tested to avoid them having CMyD. For example Dr. Jones considered an example of a 28 year old male who was confirmed diagnosis with DM. He had 2 sisters one 25 and one 21. The 21 year old sister went on to have a child with CMyD because she was not informed or tested.

Link to Article by Dr. Carter on Management of Neuromuscular Diseases