Saturday 9 August 2008

Friday 1 August 2008

Sexual and Gender Identity Disorders

History

The study of sexual deviancy began just before the turn of the 20th century as the taboo of discussing sexuality was beginning to lift. Early pioneers included Richard von Kraff-Ebing, Albert Moll, August Forel, Iwan Bloch, Magnus Hirschfield, Havelock Ellis, and Sigmund Freud. Their work was not well accepted, and they were regarded with disdain.

Several psychiatric concepts were prominent at this time. One of them was a constitutional predisposition of unknown origin called degeneration, which refers to an innate neurologic weakness that is transmitted with increased severity to future generations and produces deviations from the norm. Masturbation was blamed for a list of diseases including insanity, suicide, self-mutilation, and tuberculosis. The law of association of ideas suggests that when sex and another experience occur, one stimulus sets off the other.

Ellis worked against the prudish view of sex that existed at the time, and he advocated the decriminalization of homosexuality. Freud wrote on fetishism, masochism, and the theory of perversions. These early investigators of sexual deviation provide an important principal: "Not only must the act be studied, but also the person. The personal roots of deviance spring from an interaction of the individual's biological nature and his early life experiences."

Disorders of human behavior remain difficult to understand, identify, and treat. Few data are available, too much of our knowledge is based on speculation and unsupported theory, and societal stereotypes influence our perceptions. Good science-based research remains difficult, and monetary, ethical, and legal concerns complicate such research.

PARAP
Sexual deviation is a term applicable to a subclass of sexual disorders termed paraphilias. Paraphilias are associated with arousal in response to sexual objects or stimuli not associated with normal behavior patterns and that may interfere with the establishment of sexual relationships. In modern classification systems, the term paraphilia is preferable to sexual deviation because it clarifies the essential nature of this group of behaviors (ie, arousal in response to an inappropriate stimulus).

The American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), the prevailing resource for diagnostic criteria of paraphilias, describes the essential feature of paraphilias as recurrent, intense, sexual urges and sexually arousing fantasies generally involving nonhuman objects, the suffering or humiliation of oneself or partner, or children or other nonconsenting persons. The DSM-IV-TR describes 8 of the more commonly observed paraphilias and makes reference to several other examples. People who experience one paraphilia may also experience other paraphilias, although the paraphilia may occur as an isolated event. Commonly, people who manifest paraphilias also exhibit personality disorders, substance abuse problems, or affective disorders.

Prevalence

Paraphilias are rarely diagnosed in clinical settings. Large commercial markets in paraphiliac pornography and paraphernalia are testaments that prevalence is high. Pedophilia, voyeurism, and exhibitionism are the most commonly observed behaviors in clinics that specialize in paraphilia treatment. Sexual masochism and sexual sadism are much less commonly observed. Approximately half of patients observed in clinics for treatment of paraphilias are married.

Differentials

Nonparaphiliacs may describe nonpathological use of sexual fantasies, behaviors, or objects as stimuli for sexual excitement.

In patients with mental retardation, paraphilia should be distinguished from dementia, personality change due to general medical condition, substance intoxication, manic episode, or schizophrenia in which judgment, social skills, or impulse control are compromised.

When appropriate, public urination should be distinguished from exhibitionism.

Exhibitionism

The DSM-IV-TR diagnostic criteria for exhibitionism are as follows:


The patient reports recurrent, intense, sexual urges and sexually arousing fantasies related to exposing the genitals to a stranger. Symptoms must be present for at least 6 months.
The patient experiences significant distress or impairment in social, occupational, or other important areas of functioning because of the fantasies, urges, or behaviors.
Generally, no attempt at further sexual activity with the stranger occurs, although a desire to shock the stranger sometimes exists or the exhibitionist may have a fantasy that the observer will become sexually aroused. Onset usually occurs in persons younger than 18 years but may occur later. The disorder causes significant stress or impairment in social, occupational, or other important areas of functioning. In 1975, Rooth classified 2 types of exhibitionism: Type I is the inhibited flaccid exposer, and type II is the sociopathic exposer who may have a history of other conduct. About half of adult women have witnessed indecent exposure sometime in their lives.

Exhibitionists, whether timid or brash, feel dominated by women and resent it. By exposing themselves, exhibitionists turn the table on women, dominating rather than being dominated. Exhibitionists view this act as making women their helpless victims, rather than being helpless before them. Some researchers have suggested that exhibitionists have a fragile sense of masculinity. Threats to masculinity are countered by demonstrations of manliness.

Exhibitionists have difficulty relating to women as whole people. Rather, women are present merely to provide both gratification and proof against castration. Many exhibitionists are very prudish with their wives. They go to great efforts to never look at their wives or be seen by them in the nude. Intercourse tends to be rigid and conventional.

Common to all exhibitionists is some abnormality in handling aggression and hostility. On the one hand, they must keep their anger under tight control, yet on the other hand they may become tyrannical with their family because they feel safe from retaliation.

Male genital exhibitionism is an indicator of future sexual offenses in some individuals. In a 1980 longitudinal study, Bluglass found that 7% of exhibitionists were later convicted of contact sexual offenses, including rape.

Genital exhibitionism is rare among women. This has been explained by the differences between the sexes in the development of the castration complex and the absence of a reassuring effect from showing a penis because of anatomic differences in women. Eber in a 1977 report and Kohut in a 1978 report view female exhibitionism as a disorder of bodily narcissism.

Presentation to physicians is common and may result from a sense of guilt and an inability to control the behavior. Sometimes the behavior is revealed as the result of a criminal offense. More serious underlying pathology is suggested when preferred scenes include defecation or small children.

Fetishism

The DSM-IV-TR lists the following diagnostic criteria for fetishism:


The patient experiences recurrent and intense sexual urges and sexually arousing fantasies involving the use of nonliving objects by themselves. Symptoms must be present for at least 6 months.
The patient experiences significant distress or impairment in social, occupational, or other important areas of functioning because of the fantasies, urges, or behaviors.
The fetishes are not limited to articles of female clothing used in cross-dressing (transvestic fetishism) or devices designed for genital stimulation (eg, vibrators).
Common fetishistic objects include female underwear; rubber, plastic, or leather garments; specific articles of clothing such as shoes or boots; and bodily items such as hair, odors, or feces. The disorder is more common among males than females. Prevalence is unknown. It can often be traced from adolescence and usually persists.

In the context of psychoanalytic theory, in a 1996 publication Greenacre associates fetishism with a severe castration complex in males and a more complicated and less readily recognized set of relational reactions in females. For men, the fetish serves a defensive function, a reinforcing adjunct for a penis of uncertain potency. The fetish serves to increase the efficiency of the penis, which does not perform well without it. In women, fetishism is less common, largely because of anatomic differences that allow women to conceal inadequate sexual response more readily than men. Women can develop symptoms more comparable to male fetishism when the illusion of having a phallus has gained sufficient strength to approach delusional proportions. This occurs in rare cases in which severe disturbances in the sense of reality exist.

Treatment of the specific condition (fetish), rather than the primary underlying disorder (eg, organic pathology, personality disorder) generally is unsuccessful. A variety of treatment approaches have been tried, such as aversive conditioning, cognitive therapy, and psychotherapy.

Frotteurism

The DSM-IV-TR lists the following diagnostic criteria for frotteurism:


The patient experiences intense, recurrent, sexual urges and sexually arousing fantasies involving touching and rubbing against a nonconsensual person. Symptoms must be present for at least 6 months.
The patient experiences significant distress or impairment in social, occupational, or other important areas of functioning because of the fantasies, urges, or behaviors, or the patient has acted on the sexual urges.
Frotteurs typically act out their fantasies in crowded places (eg, public transportation vehicles, busy sidewalks), which allows for escape; the frotteur can claim that the touching was accidental. The frotteur rubs his genital area against the (usually female) victim's thighs or buttocks, or the frotteur fondles a woman's genitalia or breasts with his hands. While committing the act, the offender typically fantasizes about an exclusive, caring relationship with the victim.

Most acts occur in perpetrators aged 15-25 years, after which frequency gradually declines. Frotteurism has been noted to be equally common among older, shy, inhibited individuals. Fantasies of frotteuristic behavior without action have been reported as a stimulant to sexual arousal.

Voyeurism

The term voyeurism, from the French word meaning to see, refers to the fairly common desire to view nudity and acts of coition. Differentiating innocent enjoyment of nudity from behavior that is similar but deviant in other circumstances can be difficult.

The DSM-IV-TR diagnostic criteria for voyeurism are as follows:


The patient has recurrent and intense sexual urges and sexually arousing fantasies involving the act of observing an unsuspecting person who is naked, in the process of disrobing, or engaging in sexual activity. Symptoms must be present for at least 6 months.
The patient experiences significant distress or impairment in social, occupational, or other important areas of functioning because of the fantasies, urges, or behaviors.
When severe, the act of peeping constitutes the exclusive form of sexual activity. Onset usually is in persons younger than 15 years, and the disorder tends to be chronic. The wide extent of voyeuristic tendencies in the general population is evidenced in the common desire to indulge in exploitative activities such as live shows and pornography.

Pedophilia

The essential features of this disorder as described by the DSM-IV-TR include the following:


The patient reports recurrent and intense sexually arousing fantasies, sexual urges, or behaviors involving sexual activity with a prepubescent child or children, generally aged 13 years or younger.
Pedophiles must be aged 16 years or older and be at least 5 years older than the victim.
The disorder causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
The clinician should specify if the person is attracted to males, females, or both; if the acts are limited to incest; and if the patient is attracted to children only (exclusive type) or both children and adults (nonexclusive type).
While female pedophiles are considered to be rare, discrepancies between the numbers of male and female offenders are tied to sexual stereotypes. Masculinity connotes sexual qualities, while femininity connotes maternal qualities and nurturance. When a female pets a child, she is nurturing. When a male pets a child, he is molesting. The majority of men who have had sexual contact with a woman when they were boys viewed it positively rather than negatively. Consequently, these acts were probably unreported. In one study, 16% of college males and 46% of prisoners reported having had sexual contact with older females, and half of the encounters involved intercourse. Mean age of males at the time of sexual contact was 12 years, and the females with whom they were involved were aged 20-30 years.

Many pedophiles have a personal history of unstable parent-child relationships as children and sexual abuse. The majority of pedophiles have a clear sexual preference. The undifferentiated or bisexual group accounts for only 5-25% of pedophiles. Most studies indicate that 60-90% of incidents of abuse involve girls.

Great variation exists among men who use children sexually. One third to one half prefer children as sexual partners. Others are attracted to children but act on their impulses only under stress. Some, who typically are younger than 30 years, are sociosexually underdeveloped, lack age-appropriate experience, and have feelings of shyness and inferiority. Unable to attain adult female contact, they continue prepubescent sexual patterns. Amoral delinquent youths (younger than pedophiles proper), lacking control when aroused, use whoever is close at hand. Patients with the situational type of pedophilia have no special preference for children, although they have sexual contact with children because of convenience or coincidence. Contact typically is brief and nonrecurrent. A residual category of offenders includes people with mental retardation, psychosis, alcoholism, senility, or dementia.

Approximately 37% of sexual assault victims reported to law enforcement agencies were juveniles ( <18 y); 34% of all victims were younger than 12 years. One in 7 victims is younger than 6 years. Forty percent of offenders who victimized children younger than 6 years were juveniles ( <18 y).

Sexual masochism

The essential features of this disorder as described by the DSM-IV-TR include the following:


The patient reports recurrent and intense sexual urges and sexually arousing fantasies involving the act (real, not simulated) of being humiliated, beaten, bound, or otherwise made to suffer. Symptoms must be present for at least 6 months.
The fantasies, urges, or behaviors cause significant distress or impairment in social, occupational, or other important areas of functioning.
Masochistic acts commonly involve a wide range of activities, such as restraint, blindfolding, beating, electrical shock, cutting, piercing, and humiliation (eg, being urinated or defecated on, forced to bark, verbally abused, forced to cross-dress). Some sexual masochists inflict pain through self-mutilation, and some engage in group activity or use services provided by prostitutes.

Hypoxyphilia is a dangerous form of masochism that involves sexual arousal by oxygen deprivation achieved by means of chest compression, noose, ligature, plastic bag, mask, or chemicals. Oxygen deprivation may be accomplished alone or with a partner. Data from the United States, England, Australia, and Canada indicate that 1-2 deaths per million population are reported each year.

Some sexually masochistic males also exhibit fetishism, transvestic fetishism, or sexual sadism. Masochistic sexual fantasies are likely present in childhood. Masochistic activities commonly begin by early adulthood, tend to be chronic, and the same act is generally repeated. Some individuals increase the severity of the act over time, which may lead to injury or death.

In 1926, Sadger observed a common association between homosexuality and masochism. In a 1977 report, Spengler found that 38% of exclusive homosexuals were sadomasochists, which provides some support for Sadger's observation.

Ritualized behavior is a noted feature of masochistic scenes; the slightest deviation from the script may result in failure to achieve the desired result. This feature is also viewed as a mechanism through which the masochist maintains control.

Sexual sadism

The DSM-IV-TR diagnostic criteria for sexual sadism are as follows:


The patient reports recurrent and intense sexual urges and sexually arousing fantasies involving the act (real, not simulated) in which the psychological or physical suffering (including humiliation) of one person is sexually arousing to another person. Symptoms must be present for at least 6 months.
The fantasies, urges, or behaviors cause significant distress or impairment in social, occupational, or other important areas of functioning.
Sadistic fantasies or acts may involve activities such as dominance, restraint, blindfolding, beating, pinching, burning, electrical shock, rape, cutting, stabbing, strangulation, torture, mutilation, or killing. Sadistic sexual fantasies are likely present in childhood. Onset of sadistic activities commonly occurs by early adulthood, and it tends to be chronic.

Some individuals do not increase the severity of their sadistic acts; however, severity of the sadistic acts does usually increase over time. When practiced with nonconsenting partners, the activity is likely to be repeated until the perpetrator is apprehended. When sexual sadism is severe and associated with antisocial personality disorder, victims may be seriously injured or killed.

No clear lines divide sexual sadism and sexual masochism, and the predispositions are often interchangeable. The conditions may coexist in the same individual, sometimes in association with other paraphilias. This relationship is supported by the finding that those who entertain masochistic fantasies also engage in sadistic fantasies. In the context of psychoanalytic theory, Panken in a 1973 publication does not find that the conditions coexist in an individual and claims that the dynamics are different.

Transvestic fetishism

Transvestic fetishism is defined by DSM-IV-TR diagnostic criteria as follows:


The patient is a heterosexual male who has recurrent, intense, sexually arousing fantasies, urges, or behaviors involving cross-dressing. Symptoms must be present for at least 6 months.
These fantasies, urges, or behaviors cause significant distress or impairment in social, occupational, or other important areas of functioning.
If gender dysphoria is present, it should be specified.
Fetishistic transvestism is essentially unheard of in females. Women may cross-dress, but no literature (English) describes cross-dressing females who become sexually excited by the activity.

Other paraphilias

Sexual arousal may be obtained from a wide array of additional behaviors. Some are provided with the assistance of prostitutes, others find willing partners when needed. Other paraphilias include the following:


Scatologia (obscene phone calls)
Necrophilia (corpses)
Partialism (exclusive focus on part of body)
Zoophilia (animals)
Coprophilia (feces)
Klismaphilia (enemas)
Urophilia (urine)


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Botulism

Botulism is an acute neurologic disorder with potentially life-threatening neuroparalysis that is caused by a neurotoxin produced by Clostridium botulinum (CB). The toxin binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junctions. Toxin binding blocks acetylcholine release, resulting in weakness, flaccid paralysis, and (often) respiratory arrest. Cure occurs following sprouting of new nerve terminals.

The 3 main clinical presentations of botulism include infant, food-borne, and wound. Additionally, because of the potency of the toxin, the possibility of botulism as a bioterrorism agent or biological weapon is a great concern.

Infant botulism (IB) arises from ingested botulism spores that germinate in the intestine and produce toxin. These spores typically come from bee honey or the environment. Most infants fully recover with supportive treatment; the infant mortality rate is less than 1%. Improperly canned or home-prepared foods are common sources of the toxin that can result in food-borne botulism (FBB). Wound botulism (WB) results from contamination of the wound with toxin-producing CB. FBB and WB occur predominantly in adults and are the focus of this article.

CB is an anaerobic gram-positive rod that survives in soil and marine sediment by forming spores. Under anaerobic conditions that permit germination, it synthesizes and releases a potent exotoxin. Microbiologically, the organism stains gram-positive in cultures less than 18 hours old. The organism may stain gram-negative after 18 hours of incubation, potentially complicating attempts at diagnosis. On a molecular weight basis, botulinum toxins are the most potent toxins known.

Eight antigenically distinct CB toxins are known, including A, B, C (alpha), C (beta), D, E, F, and G. Each strain of CB is limited to producing a single toxin type. Types A, B, E, and (rarely) F cause human disease. Toxins A and B are the most potent, and the consumption of small amounts of food contaminated with them has resulted in full-blown disease. During the last 20 years, toxin A has been the most frequent cause of food-borne outbreaks; toxins B and E follow in frequency. In 15% of CB outbreaks, the toxin type is not determined. Toxins C and D cause disease in a variety of animals. Type G toxin has been associated with sudden death but not with neuroparalytic illness. It was isolated from autopsy material from 5 patients in Switzerland in 1977.

Pathophysiology
The mechanism of action involves toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers. This is accomplished by either inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions or by binding acetylcholine itself. Toxins are absorbed from the stomach and small intestine where they are not denatured by digestive enzymes. Subsequently, they are hematogenously disseminated and block neuromuscular transmission in cholinergic nerve fibers. The nervous, gastrointestinal, endocrine, and metabolic systems are predominantly affected. Because the motor end plate responds to acetylcholine, botulinum toxin ingestion results in hypotonia that manifests as descending symmetric flaccid paralysis and is usually associated with gastrointestinal symptoms of nausea, vomiting, and diarrhea. Cranial nerves are affected early in the course of disease. Later complications include paralytic ileus, severe constipation, and urinary retention.

WB results when wounds are contaminated with CB spores. It has occurred (1) after traumatic injury that involved soil contamination, (2) among injection drug users, particularly those who use black-tar heroin, and (3) after cesarean delivery. The wound may appear deceptively benign. Traumatized and devitalized tissue provides an anaerobic medium for the spores to germinate into vegetative organisms and produce neurotoxin, which then disseminates hematogenously. The nervous, endocrine, and metabolic systems are predominantly affected. Symptoms develop after an incubation period of 4-14 days, with a mean of 10 days. The clinical symptoms of WB are similar to those of FBB except that gastrointestinal symptoms (including nausea, vomiting, diarrhea) are uncommon.

Frequency
United States
The frequency is 0.034 cases out of 100,000 population, of which nearly 75% are associated with IB.

FBB incidences total 24 cases per year. WB incidences total 3 cases per year and 3 cases per year from the young adult cohort (aged 18-25 y). IB incidences total 71 cases per year, with a mean age of 3 months. FBB incidence totals 24 cases per year drawn from all age cohorts.

Toxin A is found predominantly west of the Mississippi River. Toxin B is found most commonly in the eastern United States. Toxin E is found in northern latitudes, such as the Pacific Northwest, the Great Lakes region, and Alaska. The native peoples have some of the highest rates of botulism in the world. Toxin E outbreaks frequently are associated with fish products.

International
Human botulism is found worldwide. Spores from organisms producing type A or B toxins are distributed widely in the soil and have been found throughout the world. Toxin type B commonly is found in Europe. Toxin G originally was isolated in Switzerland.

Mortality/Morbidity

Mortality rates vary according to age of the patient and the type of botulism observed. In FBB, a 25% mortality rate exists overall; however, the rate is 10% in patients younger than 20 years. In WB, the mortality rate varies (15-17%); in IB, the mortality rate usually is less than 1%.
The recovery period from botulism often is quite long (30-100 d). Some patients demonstrate residual weakness or autonomic dysfunction for 1 year after the onset of the illness. However, full neurologic recovery is usual. Permanent deficits may occur in those who sustain significant hypoxic insults.

Sex
Males present more frequently with WB than females. Males and females present with FBB in equal numbers.

Age
FBB and WB predominately occur in adults.


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Diabetes Mellitus, Type 1

Diabetes mellitus (DM) is a multisystem disease with both biochemical and anatomical consequences. It is a chronic disease of carbohydrate, fat, and protein metabolism caused by the lack of insulin. In type 1 diabetes, insulin is functionally absent because of the destruction of the beta cells of the pancreas. Type 1 DM occurs most commonly in juveniles but can occur in adults, especially in those in their late 30s and early 40s. Unlike people with type 2 DM, those with type 1 DM generally are not obese and may present initially with diabetic ketoacidosis (DKA).

Pathophysiology
Type 1 DM is a catabolic disorder in which circulating insulin is very low or absent, plasma glucagon is elevated, and the pancreatic beta cells fail to respond to all insulin-secretory stimuli. Patients need exogenous insulin to reverse this catabolic condition, prevent ketosis, decrease hyperglucagonemia, and normalize lipid and protein metabolism.

Type 1 DM is an autoimmune disease. The pancreas shows lymphocytic infiltration and destruction of insulin-secreting cells of the islets of Langerhans, causing insulin deficiency. Approximately 85% of patients have circulating islet cell antibodies, and the majority also have detectable anti-insulin antibodies before receiving insulin therapy. Most islet cell antibodies are directed against glutamic acid decarboxylase (GAD) within pancreatic B cells.

One theory regarding the etiology of type 1 DM is that it results from damage to pancreatic beta cells from an infectious or environmental agent. It triggers the immune system in a genetically susceptible individual to develop an autoimmune response against altered pancreatic beta cell antigens or molecules in beta cells that resemble a viral protein. Currently, autoimmunity is considered the major factor in the pathophysiology of type 1 DM. Prevalence is increased in patients with other autoimmune diseases, such as Graves disease, Hashimoto thyroiditis, and Addison disease. Approximately 95% of patients with type 1 DM have either human leukocyte antigen (HLA)-DR3 or HLA-DR4. HLA-DQs are considered specific markers of type 1 DM susceptibility.

Environmental agents that have been hypothesized to induce an attack on beta cell function include viruses (eg, mumps, rubella, Coxsackie B4), toxic chemicals, exposure to cow's milk in infancy, and cytotoxins.

Recent evidence suggests a role for vitamin D in the pathogenesis and prevention of diabetes mellitus.


Frequency
United States
Roughly 5-15% of all cases of diabetes are type 1 DM. It is the most common metabolic disease of childhood, with a yearly incidence of 15 cases per 100,000 people younger than 18 years. Approximately 1 million Americans have type 1 DM, and physicians diagnose 10,000 new cases every year.


According to the American Diabetes Association, there are 20.8 million children and adults in the United States, or 7% of the population, who have diabetes. While an estimated 14.6 million have been diagnosed, unfortunately, 6.2 million people (or nearly one-third) are undiagnosed. Fifty-four million people are prediabetes status. In people younger than 20 years, 176,500 cases, or 0.22% of all people in this age group, have diabetes. About one in every 400-600 children and adolescents has type 1 DM. Two million adolescents (or 1 in 6 overweight adolescents) aged 12-19 years have prediabetes status. In people aged 20 years or older, 1.5 million new cases of diabetes were diagnosed in 2005.


International
Scandinavia has the highest prevalence rates for type 1 DM (ie, approximately 20% of the total number of people with DM), while China and Japan have the lowest prevalence rates, with less than 1% of all people with diabetes. Some of these differences may relate to definitional issues and the completeness of reporting.

Mortality/Morbidity
Type 1 DM is associated with a high morbidity and premature mortality due to complications. The annual financial cost from diabetes overall exceeds $100 billion, almost $1 of every $7 dollars of US health expenditures in terms of medical care and loss of productivity. Advances in treatment that permit tight glycemic control and control of comorbidities (hyperlipidemia) can greatly reduce the incidence of microvascular and macrovascular complications.

As a result of these complications, people with diabetes have an increased risk of developing ischemic heart disease, cerebral vascular disease, peripheral vascular disease with gangrene of lower limbs, chronic renal disease, reduced visual acuity and blindness, and autonomic and peripheral neuropathy.

Race
Type 1 DM is more common among non-Hispanic whites, followed by African Americans and Hispanic Americans. It is comparatively uncommon among Asians.

Sex
Type 1 DM is more common in men than in women.

Age
Type 1 DM usually starts in children aged 4 years or older, with the peak incidence of onset at age 11-13 years, coinciding with early adolescence and puberty. Also, a relatively high incidence exists in people in their late 30s and early 40s, when it tends to present in a less aggressive manner, ie, early hyperglycemia without ketoacidosis and gradual onset of ketosis.


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Grey Matter - from the writers of Grey's Anatomy